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Review Open Access

The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review)

  • Authors:
    • Li Liu
    • Li Yang
    • Hongmin Li
    • Tianlu Shang
    • Lihan Liu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, The Third Affiliated Hospital of Gansu University of Chinese Medicine, Baiyin, Gansu 730900, P.R. China, Department of Oncology, The Third Affiliated Hospital of Gansu University of Chinese Medicine, Baiyin, Gansu 730900, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 11
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    Published online on: November 26, 2025
       https://doi.org/10.3892/ijo.2025.5824
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Abstract

Lung cancer remains a leading cause of cancer‑related death. Despite advances in targeted therapies and immunotherapy, treatment outcomes remain suboptimal due to tumor heterogeneity and therapeutic resistance. The tumor microenvironment (TME), a dynamic ecosystem comprising immune cells, stromal components, extracellular matrix and bioactive molecules, serves a critical role in promoting tumor progression and resistance. The present review comprehensively analyzes the molecular mechanisms underlying TME‑mediated immune evasion, and resistance to chemotherapy, radiotherapy and immunotherapy. In addition, emerging therapeutic strategies targeting the TME are highlighted, such as immune microenvironment modulation, metabolic and epigenetic interventions, and nanotechnology‑based drug delivery systems. By integrating multi‑omics datasets and spatial transcriptomics, TME‑directed interventions are moving toward biomarker‑guided, personalized regimens.
View Figures

Figure 1

TME composition and interactions in
lung cancer. Components of the TME, including immune cells (such as
TAMs, MDSCs and Tregs), stromal cells (for example, CAFs and
endothelial cells), ECM and soluble factors (cytokines, chemokines
and growth factors), are shown, as are the interaction between
these components. For example, TAMs secrete IL-10 and TGF-β, thus
inhibiting antitumor immune responses, and CAFs promote tumor
progression by secreting ECM components and growth factors. This
figure was created using Figdraw (www.figdraw.com, ID: YTYOW4a999). CAFs,
cancer-associated fibroblasts; ECM, extracellular matrix; IL-10,
interleukin-10; MDSCs, myeloid-derived suppressor cells; PD-L1,
programmed death-ligand 1; TAMs, tumor-associated macrophages; TME,
tumor microenvironment; TGF-β, transforming growth factor-β; Tregs,
regulatory T cells.

Figure 2

Mechanisms of therapeutic resistance
in the TME. The mechanism by which the TME drives treatment
resistance is shown, including immune escape mechanisms (such as
PD-L1 upregulation, the LAG-3/FGL1 axis and the role of VISTA),
metabolic reprogramming (for example, hypoxia-induced autophagy and
immunosuppression due to lactic acid accumulation) and epigenetic
regulation (such as RNA modification and the role of lncRNAs). This
figure was created using Figdraw (www.figdraw.com, ID: STSWAa4006). CSCs, cancer stem
cells; FGL1, fibrinogen-like protein 1; LAG-3,
lymphocyte-activation gene 3; lncRNA, long non-coding RNA; PD-L1,
programmed death-ligand 1; TME, tumor microenvironment; VISTA,
V-type immunoglobulin domain-containing suppressor of T-cell
activation.
View References

1 

Wéber A, Morgan E, Vignat J, Laversanne M, Pizzato M, Rumgay H, Singh D, Nagy P, Kenessey I, Soerjomataram I and Bray F: Lung cancer mortality in the wake of the changing smoking epidemic: A descriptive study of the global burden in 2020 and 2040. BMJ Open. 13:e0653032023. View Article : Google Scholar : PubMed/NCBI

2 

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I and Jemal A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 74:229–263. 2024.PubMed/NCBI

3 

Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M and Miller VA: Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: Distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 17:1616–1622. 2011. View Article : Google Scholar

4 

Miyata H, Shigeto H, Ikeya T, Ashizawa T, Iizuka A, Kikuchi Y, Maeda C, Kanematsu A, Yamashita K, Urakami K, et al: Localization of epidermal growth factor receptor-mutations using PNA: DNA probes in clinical specimens from patients with non-small cell lung cancer. Sci Rep. 15:113142025. View Article : Google Scholar

5 

Son B, Lee S, Youn H, Kim E, Kim W and Youn B: The role of tumor microenvironment in therapeutic resistance. Oncotarget. 8:3933–3945. 2017. View Article : Google Scholar :

6 

Yu H, Zhang W, Xu XR and Chen S: Drug resistance related genes in lung adenocarcinoma predict patient prognosis and influence the tumor microenvironment. Sci Rep. 13:96822023. View Article : Google Scholar : PubMed/NCBI

7 

Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, et al: Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 384:2371–2381. 2021. View Article : Google Scholar : PubMed/NCBI

8 

Said SS and Ibrahim WN: Cancer resistance to immunotherapy: Comprehensive insights with future perspectives. Pharmaceutics. 15:11432023. View Article : Google Scholar : PubMed/NCBI

9 

Glaviano A, Lau HS, Carter LM, Lee EHC, Lam HY, Okina E, Tan DJJ, Tan W, Ang HL, Carbone D, et al: Harnessing the tumor microenvironment: Targeted cancer therapies through modulation of epithelial-mesenchymal transition. J Hematol Oncol. 18:62025. View Article : Google Scholar : PubMed/NCBI

10 

Tian Y, Yang Y, He L, Yu X, Zhou H and Wang J: Exploring the tumor microenvironment of breast cancer to develop a prognostic model and predict immunotherapy responses. Sci Rep. 15:125692025. View Article : Google Scholar : PubMed/NCBI

11 

Tan Z, Xue H, Sun Y, Zhang C, Song Y and Qi Y: The role of tumor inflammatory microenvironment in lung cancer. Front Pharmacol. 12:6886252021. View Article : Google Scholar : PubMed/NCBI

12 

Liu Y, Liang J, Zhang Y and Guo Q: Drug resistance and tumor immune microenvironment: An overview of current understandings (Review). Int J Oncol. 65:962024. View Article : Google Scholar : PubMed/NCBI

13 

Heydenreich B, Bellinghausen I, Lorenz S, Henmar H, Strand D, Würtzen PA and Saloga J: Reduced in vitro T-cell responses induced by glutaraldehyde-modified allergen extracts are caused mainly by retarded internalization of dendritic cells. Immunology. 136:208–217. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Mai Z, Lin Y, Lin P, Zhao X and Cui L: Modulating extracellular matrix stiffness: A strategic approach to boost cancer immunotherapy. Cell Death Dis. 15:3072024. View Article : Google Scholar : PubMed/NCBI

15 

Chen K, Luo L, Li Y and Yang G: Reprogramming the immune microenvironment in lung cancer. Volume. 16:16848892025.

16 

Chandra R, Ehab J, Hauptmann E, Gunturu NS, Karalis JD, Kent DO, Heid CA, Reznik SI, Sarkaria IS, Huang H, et al: The current state of tumor Microenvironment-specific therapies for Non-small cell lung cancer. Cancers (Basel). 17:17322025. View Article : Google Scholar : PubMed/NCBI

17 

He ZN, Zhang CY, Zhao YW, He SL, Li Y, Shi BL, Hu JQ, Qi RZ and Hua BJ: Regulation of T cells by myeloid-derived suppressor cells: Emerging immunosuppressor in lung cancer. Discov Oncol. 14:1852023. View Article : Google Scholar : PubMed/NCBI

18 

Lim JU, Lee E, Lee SY, Cho HJ, Ahn DH, Hwang Y, Choi JY, Yeo CD, Park CK and Kim SJ: Current literature review on the tumor immune micro-environment, its heterogeneity and future perspectives in treatment of advanced non-small cell lung cancer. Transl Lung Cancer Res. 12:857–876. 2023. View Article : Google Scholar : PubMed/NCBI

19 

Genova C, Dellepiane C, Carrega P, Sommariva S, Ferlazzo G, Pronzato P, Gangemi R, Filaci G, Coco S and Croce M: Therapeutic implications of tumor microenvironment in lung cancer: Focus on immune checkpoint blockade. Front Immunol. 12:7994552021. View Article : Google Scholar

20 

Cao Q, Li C, Li Y, Kong X, Wang S and Ma J: Tumor microenvironment and drug resistance in lung adenocarcinoma: Molecular mechanisms, prognostic implications, and therapeutic strategies. Discov Oncol. 16:2382025. View Article : Google Scholar : PubMed/NCBI

21 

Chu X, Tian Y and Lv C: Decoding the spatiotemporal heterogeneity of Tumor-associated macrophages. Mol Cancer. 23:1502024. View Article : Google Scholar : PubMed/NCBI

22 

Mei S, Zhang H, Hirz T, Jeffries NE, Xu Y, Baryawno N, Wu S, Wu CL, Patnaik A, Saylor PJ, et al: Single-cell and spatial transcriptomics reveal a Tumor-associated macrophage subpopulation that mediates prostate cancer progression and metastasis. Mol Cancer Res. 23:653–665. 2025. View Article : Google Scholar : PubMed/NCBI

23 

Ashrafi A, Akter Z, Modareszadeh P, Modareszadeh P, Berisha E, Alemi PS, Chacon Castro MDC, Deese AR and Zhang L: Current landscape of therapeutic resistance in lung cancer and promising strategies to overcome resistance. Cancers (Basel). 14:45622022. View Article : Google Scholar : PubMed/NCBI

24 

Guo T and Xu J: Cancer-associated fibroblasts: A versatile mediator in tumor progression, metastasis, and targeted therapy. Cancer Metastasis Rev. 43:1095–1116. 2024. View Article : Google Scholar : PubMed/NCBI

25 

Wu C, Gu J, Gu H, Zhang X, Zhang X and Ji R: The recent advances of cancer associated fibroblasts in cancer progression and therapy. Front Oncol. 12:10088432022. View Article : Google Scholar : PubMed/NCBI

26 

Papavassiliou KA, Sofianidi AA, Gogou VA and Papavassiliou AG: Drugging the tumor microenvironment epigenome for therapeutic interventions in NSCLC. J Cancer. 16:1832–1835. 2025. View Article : Google Scholar : PubMed/NCBI

27 

Tong L, Jiménez-Cortegana C, Tay AHM, Wickström S, Galluzzi L and Lundqvist A: NK cells and solid tumors: Therapeutic potential and persisting obstacles. Mol Cancer. 21:2062022. View Article : Google Scholar : PubMed/NCBI

28 

Liu J, Wu M, Yang Y, Wang Z, He S, Tian X and Wang H: γδ T cells and the PD-1/PD-L1 axis: A love-hate relationship in the tumor microenvironment. J Transl Med. 22:5532024. View Article : Google Scholar

29 

Mancini A, Gentile MT, Pentimalli F, Cortellino S, Grieco M and Giordano A: Multiple aspects of matrix stiffness in cancer progression. Front Oncol. 14:14066442024. View Article : Google Scholar : PubMed/NCBI

30 

Henke E, Nandigama R and Ergün S: Extracellular matrix in the tumor microenvironment and its impact on cancer therapy. Front Mol Biosci. 6:1602019. View Article : Google Scholar

31 

Marrugal Á, Ojeda L, Paz-Ares L, Molina-Pinelo S and Ferrer I: Proteomic-based approaches for the study of cytokines in lung cancer. Dis Markers. 2016:21386272016. View Article : Google Scholar : PubMed/NCBI

32 

Zhang A, Miao K, Sun H and Deng CX: Tumor heterogeneity reshapes the tumor microenvironment to influence drug resistance. Int J Biol Sci. 18:3019–3033. 2022. View Article : Google Scholar : PubMed/NCBI

33 

Li X, Shang S, Wu M, Song Q and Chen D: Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis. Cancer Lett. 598:2170962024. View Article : Google Scholar : PubMed/NCBI

34 

Li J, Shi B, Ren X, Hu J, Li Y, He S, Zhang G, Maolan A, Sun T, Qi X, et al: Lung-intestinal axis, Shuangshen granules attenuate lung metastasis by regulating the intestinal microbiota and related metabolites. Phytomedicine. 132:1558312024. View Article : Google Scholar : PubMed/NCBI

35 

Ankudavicius V, Nikitina D, Lukosevicius R, Tilinde D, Salteniene V, Poskiene L, Miliauskas S, Skieceviciene J, Zemaitis M and Kupcinskas J: Detailed characterization of the Lung-gut microbiome axis reveals the link between PD-L1 and the microbiome in Non-Small-cell lung cancer patients. Int J Mol Sci. 25:23232024. View Article : Google Scholar : PubMed/NCBI

36 

Dong Q, Chen ES, Zhao C and Jin C: Host-Microbiome interaction in lung cancer. Front Immunol. 12:6798292021. View Article : Google Scholar : PubMed/NCBI

37 

Hunt PJ, Andújar FN, Silverman DA and Amit M: Mini-review: Trophic interactions between cancer cells and primary afferent neurons. Neurosci Lett. 746:1356582021. View Article : Google Scholar : PubMed/NCBI

38 

Hernandez S, Serrano AG and Solis Soto LM: The role of nerve fibers in the tumor Immune microenvironment of solid tumors. Adv Biol (Weinh). 6:22000462022. View Article : Google Scholar

39 

Li X, Peng X, Yang S, Wei S, Fan Q, Liu J, Yang L and Li H: Targeting tumor innervation: Premises, promises, and challenges. Cell Death Discov. 8:1312022. View Article : Google Scholar : PubMed/NCBI

40 

Yang Y, Ye WL, Zhang RN, He XS, Wang JR, Liu YX, Wang Y, Yang XM, Zhang YJ and Gan WJ: The role of TGF-β signaling pathways in cancer and its potential as a therapeutic target. Evid Based Complement Alternat Med. 2021:66752082021.

41 

Jiang C, Zhang N, Hu X and Wang H: Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms. Mol Cancer. 20:1172021. View Article : Google Scholar : PubMed/NCBI

42 

Yang J, Xu J, Wang W, Zhang B, Yu X and Shi S: Epigenetic regulation in the tumor microenvironment: Molecular mechanisms and therapeutic targets. Signal Transduct Target Ther. 8:2102023. View Article : Google Scholar : PubMed/NCBI

43 

Yu W, Hua Y, Qiu H, Hao J, Zou K, Li Z, Hu S, Guo P, Chen M, Sui S, et al: PD-L1 promotes tumor growth and progression by activating WIP and β-catenin signaling pathways and predicts poor prognosis in lung cancer. Cell Death Dis. 11:5062020. View Article : Google Scholar

44 

Xiao K, Zhang S, Peng Q, Du Y, Yao X, Ng II and Tang H: PD-L1 protects tumor-associated dendritic cells from ferroptosis during immunogenic chemotherapy. Cell Rep. 43:1148682024. View Article : Google Scholar : PubMed/NCBI

45 

Shi AP, Tang XY, Xiong YL, Zheng KF, Liu YJ, Shi XG, Lv Y, Jiang T, Ma N and Zhao JB: Immune checkpoint LAG3 and its ligand FGL1 in cancer. Front Immunol. 12:7850912021. View Article : Google Scholar

46 

Villarroel-Espindola F, Yu X, Datar I, Mani N, Sanmamed M, Velcheti V, Syrigos K, Toki M, Zhao H, Chen L, et al: Spatially resolved and quantitative analysis of VISTA/PD-1H as a novel immunotherapy target in human Non-small cell lung cancer. Clin Cancer Res. 24:1562–1573. 2018. View Article : Google Scholar :

47 

Wang S, Wang J, Chen Z, Luo J, Guo W, Sun L and Lin L: Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance. NPJ Precis Oncol. 8:312024. View Article : Google Scholar : PubMed/NCBI

48 

Li Y, Zhao L and Li XF: Hypoxia and the tumor microenvironment. Technol Cancer Res Treat. 20:153303382110363042021. View Article : Google Scholar : PubMed/NCBI

49 

Zaarour RF, Azakir B, Hajam EY, Nawafleh H, Zeinelabdin NA, Engelsen AST, Thiery J, Jamora C and Chouaib S: Role of Hypoxia-mediated autophagy in tumor cell death and survival. Cancers (Basel). 13:5332021. View Article : Google Scholar : PubMed/NCBI

50 

Sasidharan Nair V, Saleh R, Toor SM, Cyprian FS and Elkord E: Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment. Cancer Immunol Immunother. 70:2103–2121. 2021. View Article : Google Scholar : PubMed/NCBI

51 

Li X, Yan X, Wang Y, Kaur B, Han H and Yu J: The Notch signaling pathway: A potential target for cancer immunotherapy. J Hematol Oncol. 16:452023. View Article : Google Scholar : PubMed/NCBI

52 

Luo H, Liu L, Liu X, Xie Y, Huang X, Yang M, Shao C and Li D: Interleukin-33 (IL-33) promotes DNA damage-resistance in lung cancer. Cell Death Dis. 16:2742025. View Article : Google Scholar : PubMed/NCBI

53 

Boo SH and Kim YK: The emerging role of RNA modifications in the regulation of mRNA stability. Exp Mol Med. 52:400–408. 2020. View Article : Google Scholar : PubMed/NCBI

54 

Guo Y, Xie Y and Luo Y: The role of Long Non-coding RNAs in the tumor immune microenvironment. Front Immunol. 13:8510042022. View Article : Google Scholar : PubMed/NCBI

55 

Jiang J, Lu Y, Zhang F, Huang J, Ren XL and Zhang R: The emerging roles of long noncoding RNAs as hallmarks of lung cancer. Front Oncol. 11:7615822021. View Article : Google Scholar : PubMed/NCBI

56 

Entezari M, Ghanbarirad M, Taheriazam A, Sadrkhanloo M, Zabolian A, Goharrizi MASB, Hushmandi K, Aref AR, Ashrafizadeh M, Zarrabi A, et al: Long non-coding RNAs and exosomal lncRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling. Biomed Pharmacother. 150:1129632022. View Article : Google Scholar : PubMed/NCBI

57 

Tian Z, Cen L, Wei F, Dong J, Huang Y, Han Y, Wang Z, Deng J and Jiang Y: EGFR mutations in non-small cell lung cancer: Classification, characteristics and resistance to third-generation EGFR-tyrosine kinase inhibitors (Review). Oncol Lett. 30:3752025. View Article : Google Scholar : PubMed/NCBI

58 

Parente P, Parcesepe P, Covelli C, Olivieri N, Remo A, Pancione M, Latiano TP, Graziano P, Maiello E and Giordano G: Crosstalk between the tumor microenvironment and immune system in pancreatic ductal adenocarcinoma: Potential targets for new therapeutic approaches. Gastroenterol Res Pract. 2018:75306192018. View Article : Google Scholar

59 

Reichel D, Tripathi M and Perez JM: Biological effects of nanoparticles on macrophage polarization in the tumor microenvironment. Nanotheranostics. 3:66–88. 2019. View Article : Google Scholar : PubMed/NCBI

60 

Coelho MA, Strauss ME, Watterson A, Cooper S, Bhosle S, Illuzzi G, Karakoc E, Dinçer C, Vieira SF, Sharma M, et al: Base editing screens define the genetic landscape of cancer drug resistance mechanisms. Nature Genetics. 56:2479–2492. 2024. View Article : Google Scholar : PubMed/NCBI

61 

Wen Y, Zhu Y, Zhang C, Yang X, Gao Y, Li M, Yang H, Liu T and Tang H: Chronic inflammation, cancer development and immunotherapy. Front Pharmacol. 13:10401632022. View Article : Google Scholar : PubMed/NCBI

62 

Qian FF and Han BH: Mechanisms of resistance to immune checkpoint inhibitors and strategies to reverse drug resistance in lung cancer. Chin Med J (Engl). 133:2444–2455. 2020. View Article : Google Scholar : PubMed/NCBI

63 

Bagchi S, Yuan R and Engleman EG: Immune checkpoint inhibitors for the treatment of cancer: Clinical impact and mechanisms of response and resistance. Annu Rev Pathol. 16:223–249. 2021. View Article : Google Scholar

64 

Zhang M and Zhang B: Extracellular matrix stiffness: Mechanisms in tumor progression and therapeutic potential in cancer. Exp Hematol Oncol. 14:542025. View Article : Google Scholar : PubMed/NCBI

65 

Benvenuto M and Focaccetti C: Tumor microenvironment: Cellular interaction and metabolic adaptations. Int J Mol Sci. 25:36422024. View Article : Google Scholar : PubMed/NCBI

66 

Utsumi T, Mizuta H, Seto Y, Uchibori K, Nishio M, Okamoto I and Katayama R: AXL-Mediated drug resistance in ALK-rearranged NSCLC enhanced by GAS6 from macrophages and MMP11 positive fibroblasts. Cancer Sci. 116:1034–1047. 2025. View Article : Google Scholar : PubMed/NCBI

67 

Peyraud F, Guégan JP, Rey C, Lara O, Odin O, Del Castillo M, Vanhersecke L, Coindre JM, Clot E, Brunet M, et al: Spatially resolved transcriptomics reveal the determinants of primary resistance to immunotherapy in NSCLC with mature tertiary lymphoid structures. Cell Rep Med. 6:1019342025. View Article : Google Scholar : PubMed/NCBI

68 

Nishinakamura H, Shinya S, Irie T, Sakihama S, Naito T, Watanabe K, Sugiyama D, Tamiya M, Yoshida T, Hase T, et al: Coactivation of innate immune suppressive cells induces acquired resistance against combined TLR agonism and PD-1 blockade. Sci Transl Med. 17:adk31602025. View Article : Google Scholar

69 

Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, et al: Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 378:2078–2092. 2018. View Article : Google Scholar : PubMed/NCBI

70 

Cheng M and Hu S: Lung-resident γδ T cells and their roles in lung diseases. Immunology. 51:375–384. 2017. View Article : Google Scholar

71 

Subhi-Issa N, Tovar Manzano D, Pereiro Rodriguez A, Sanchez Ramon S, Perez Segura P and Ocaña A: γδ T cells: Game changers in immune cell therapy for cancer. Cancers (Basel). 17:10632025. View Article : Google Scholar

72 

Lv J, Liu Z, Ren X, Song S, Zhang Y and Wang Y: γδT cells, a key subset of T cell for cancer immunotherapy. Front Immunol. 16:15621882025. View Article : Google Scholar

73 

Jin C, Lagoudas GK, Zhao C, Bullman S, Bhutkar A, Hu B, Ameh S, Sandel D, Liang XS, Mazzilli S, et al: Commensal microbiota promote lung cancer development via γδ T cells. Cell. 176:998–1013.e16. 2019. View Article : Google Scholar

74 

Dhodapkar MV and Dhodapkar KM: Tissue-resident memory-like T cells in tumor immunity: Clinical implications. Semin Immunol. 49:1014152020. View Article : Google Scholar : PubMed/NCBI

75 

Hofmann M, Thimme R and Schamel WW: PD-1 and LAG-3: Synergistic fostering of T cell exhaustion. Signal Transduct Target Ther. 9:2912024. View Article : Google Scholar : PubMed/NCBI

76 

Ducimetière L, Vermeer M and Tugues S: The interplay between innate lymphoid cells and the tumor microenvironment. Front Immunol. 10:28952019. View Article : Google Scholar

77 

Yuan X, Rasul F, Nashan B and Sun C: Innate lymphoid cells and cancer: Role in tumor progression and inhibition. Eur J Immunol. 51:2188–2205. 2021. View Article : Google Scholar : PubMed/NCBI

78 

Ebid N, Sharaky M, Elkhoely A, El Morsy EM and Saad SY: Cross-talk signaling between non-small cell lung cancer cell lines and fibroblasts attenuates the cytotoxic effect of cisplatin. J Biochem Mol Toxicol. 39:e702012025. View Article : Google Scholar : PubMed/NCBI

79 

Zhang Q, Luo Y, Qian B, Cao X, Xu C, Guo K, Wan R, Jiang Y, Wang T, Mei Z, et al: A systematic pan-cancer analysis identifies LDHA as a novel predictor for immunological, prognostic, and immunotherapy resistance. Aging (Albany NY). 16:8000–8018. 2024.PubMed/NCBI

80 

Wang Z, Yan N, Sheng H, Xiao Y, Sun J and Cao C: Single-cell transcriptomic analysis reveals an immunosuppressive network between POSTN CAFs and ACKR1 ECs in TKI-resistant lung cancer. Cancer Genomics Proteomics. 21:65–78. 2024. View Article : Google Scholar :

81 

Wang Y, Meraz IM, Qudratullah M, Kotagiri S, Han Y, Xi Y, Wang J and Lissanu Y: SMARCA4 mutation induces tumor cell-intrinsic defects in enhancer landscape and resistance to immunotherapy. bioRxiv. Jun 22–2024. View Article : Google Scholar

82 

Huang H, Zhu X, Yu Y, Li Z, Yang Y, Xia L and Lu S: EGFR mutations induce the suppression of CD8+ T cell and anti-PD-1 resistance via ERK1/2-p90RSK-TGF-β axis in non-small cell lung cancer. J Transl Med. 22:6532024. View Article : Google Scholar

83 

Kobayashi N, Katakura S, Fukuda N, Somekawa K, Kaneko A and Kaneko T: The impact of bevacizumab and miR200c on EMT and EGFR-TKI resistance in EGFR-mutant lung cancer organoids. Genes (Basel). 15:16242024. View Article : Google Scholar

84 

Tan J, Zhu L, Shi J, Zhang J, Kuang J, Guo Q, Zhu X, Chen Y, Zhou C and Gao X: Evaluation of drug resistance for EGFR-TKIs in lung cancer via multicellular lung-on-a-chip. Eur J Pharm Sci. 199:1068052024. View Article : Google Scholar : PubMed/NCBI

85 

Pan X, Qian H, Sun Z, Yi Q, Liu Y, Lan G, Chen J and Wang G: Investigating the role of disulfidptosis related genes in radiotherapy resistance of lung adenocarcinoma. Front Med (Lausanne). 11:14730802024. View Article : Google Scholar : PubMed/NCBI

86 

Han R, Guo H, Shi J, Zhao S, Jia Y, Liu X, Liu Y, Cheng L, Zhao C, Li X and Zhou C: Osimertinib in combination with anti-angiogenesis therapy presents a promising option for osimertinib-resistant non-small cell lung cancer. BMC Med. 22:1742024. View Article : Google Scholar : PubMed/NCBI

87 

Shen A, Sun Y, Wang G, Meng X, Ren X, Wan Q, Lv Q, Wang X, Ni J, Li M, et al: An adaptable nanoprobe integrated with quantitative T1-Mapping MRI for accurate differential diagnosis of Multidrug-resistant lung cancer. Adv Healthc Mater. 12:e23006842023. View Article : Google Scholar

88 

Lu J, Li J, Lin Z, Li H, Lou L, Ding W, Ouyang S, Wu Y, Wen Y, Chen X, et al: Reprogramming of TAMs via the STAT3/CD47-SIRPα axis promotes acquired resistance to EGFR-TKIs in lung cancer. Cancer Lett. 564:2162052023. View Article : Google Scholar

89 

Yuan Y: Spatial heterogeneity in the tumor microenvironment. Cold Spring Harb Perspect Med. 6:a0265832016. View Article : Google Scholar : PubMed/NCBI

90 

Wang Y, Liu B, Min Q, Yang X, Yan S, Ma Y, Li S, Fan J, Wang Y, Dong B, et al: Spatial transcriptomics delineates molecular features and cellular plasticity in lung adenocarcinoma progression. Cell Discovery. 9:962023. View Article : Google Scholar : PubMed/NCBI

91 

Zhang JT, Zhang J, Wang SR, Yan LX, Qin J, Yin K, Chu XP, Wang MM, Hong HZ, Lv ZY, et al: Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma. iScience. 26:1076992023. View Article : Google Scholar : PubMed/NCBI

92 

Zhang J, Song C, Tian Y and Yang X: Single-cell RNA sequencing in lung cancer: Revealing phenotype shaping of stromal cells in the microenvironment. Front Immunol. 12:8020802021. View Article : Google Scholar

93 

Joo MS, Pyo KH, Chung JM and Cho BC: Artificial intelligence-based non-small cell lung cancer transcriptome RNA-sequence analysis technology selection guide. Front Bioeng Biotechnol. 11:10819502023. View Article : Google Scholar : PubMed/NCBI

94 

Xie L, Xie D, Du Z, Xue S, Wang K, Yu X, Liu X, Peng Q and Fang C: A novel therapeutic outlook: Classification, applications and challenges of inhalable micron/nanoparticle drug delivery systems in lung cancer (Review). Int J Oncol. 64:382024. View Article : Google Scholar : PubMed/NCBI

95 

Hu M and Huang L: Strategies targeting tumor immune and stromal microenvironment and their clinical relevance. Adv Drug Deliv Rev. 183:1141372022. View Article : Google Scholar : PubMed/NCBI

96 

Qian W, Zhao M, Wang R and Li H: Fibrinogen-like protein 1 (FGL1): The next immune checkpoint target. J Hematol Oncol. 14:1472021. View Article : Google Scholar : PubMed/NCBI

97 

Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J, Chen L, Chen Y, Zhu G, Yin W, et al: Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell. 176:334–347.e12. 2019. View Article : Google Scholar

98 

Miao L, Wang Y, Lin CM, Xiong Y, Chen N, Zhang L, Kim WY and Huang L: Nanoparticle modulation of the tumor microenvironment enhances therapeutic efficacy of cisplatin. J Control Release. 217:27–41. 2015. View Article : Google Scholar : PubMed/NCBI

99 

Runa F, Hamalian S, Meade K, Shisgal P, Gray PC and Kelber JA: Tumor microenvironment heterogeneity: Challenges and opportunities. Curr Mol Biol Rep. 3:218–229. 2017. View Article : Google Scholar

100 

Guan XY, Guan XL and Jiao ZY: Improving therapeutic resistance: Beginning with targeting the tumor microenvironment. J Chemother. 34:492–516. 2022. View Article : Google Scholar

101 

Lu J and Ramirez RA: The role of checkpoint inhibition in Non-small cell lung cancer. Ochsner J. 17:379–387. 2017.PubMed/NCBI

102 

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, et al: Pembrolizumab versus chemotherapy for PD-L1-positive Non-small-cell lung cancer. N Engl J Med. 375:1823–1833. 2016. View Article : Google Scholar : PubMed/NCBI

103 

Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, et al: Nivolumab plus ipilimumab in advanced Non-Small-Cell lung cancer. N Engl J Med. 381:2020–2031. 2019. View Article : Google Scholar : PubMed/NCBI

104 

Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, et al: Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 378:1976–1986. 2018. View Article : Google Scholar : PubMed/NCBI

105 

Niemeijer AN, Leung D, Huisman MC, Bahce I, Hoekstra OS, van Dongen GAMS, Boellaard R, Du S, Hayes W, Smith R, et al: Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer. Nat Commun. 9:46642018. View Article : Google Scholar : PubMed/NCBI

106 

Zhang Y, Zhou H and Zhang L: Which is the optimal immunotherapy for advanced squamous non-small-cell lung cancer in combination with chemotherapy: Anti-PD-1 or anti-PD-L1? J Immunother Cancer. 6:1352018. View Article : Google Scholar : PubMed/NCBI

107 

Bozorgmehr F, Hommertgen A, Krisam J, Lasitschka F, Kuon J, Maenz M, Huber PE, König L, Kieser M, Debus J, et al: Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer-study protocol of the FORCE trial. BMC Cancer. 19:10742019. View Article : Google Scholar

108 

Zhao S, Ren S, Jiang T, Zhu B, Li X, Zhao C, Jia Y, Shi J, Zhang L, Liu X, et al: Low-Dose apatinib optimizes tumor microenvironment and potentiates antitumor effect of PD-1/PD-L1 blockade in lung cancer. Cancer Immunol Res. 7:630–643. 2019. View Article : Google Scholar : PubMed/NCBI

109 

Leighl NB, Redman MW, Rizvi N, Hirsch FR, Mack PC, Schwartz LH, Wade JL, Irvin WJ, Reddy SC, Crawford J, et al: Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760). J Immunother Cancer. 9:e0029732021. View Article : Google Scholar : PubMed/NCBI

110 

Ott PA, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N, Margolin K, Awad MM, Hellmann MD, Lin JJ, et al: A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer. Cell. 183:347–362.e24. 2020. View Article : Google Scholar : PubMed/NCBI

111 

Awad MM, Govindan R, Balogh KN, Spigel DR, Garon EB, Bushway ME, Poran A, Sheen JH, Kohler V, Esaulova E, et al: Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer. Cancer Cell. 40:1010–1026.e11. 2022. View Article : Google Scholar : PubMed/NCBI

112 

Li JH, Tian F, Qiu CS, Chen WJ, Xu DX, Yang LQ and Li RJ: Relevant studies on effect of Fuzheng Sanjie recipe in regulating immune microenvironment remodeling of TAMs in Lewis lung cancer mice. Zhongguo Zhong Yao Za Zhi. 40:1161–1165. 2015.In Chinese. PubMed/NCBI

113 

Gao J, Bi L, Jiang YC, Yang Y, Li BY and Chen WP: Effect of water extract of ginseng on biological bechaviors of lung cancer A549 cells and the expression of F-actin in Co-culture system of TAMs and A549 cells. Zhongguo Zhong Xi Yi Jie He Za Zhi. 37:345–350. 2017.In Chinese. PubMed/NCBI

114 

Wen X, Wang Y, Su C, You Y, Jiang Z, Zhu D and Fan Q: Integrating Multi-omics technologies with traditional Chinese medicine to enhance cancer research and treatment. QJM. Apr 29–2025.Epub ahead of print. View Article : Google Scholar

115 

Li Y, Cao F, Li M, Li P, Yu Y, Xiang L, Xu T, Lei J, Tai YY, Zhu J, et al: Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages. J Exp Clin Cancer Res. 37:2592018. View Article : Google Scholar : PubMed/NCBI

116 

Sarnaik AA, Hwu P, Mulé JJ and Pilon-Thomas S: Tumor-infiltrating lymphocytes: A new hope. Cancer Cell. 42:1315–1318. 2024. View Article : Google Scholar : PubMed/NCBI

117 

Stachowiak M, Becker WJ, Olkhanud PB, Moreno PA, Markowicz S, Berzofsky JA and Sarnowska E: Cancer cells accelerate exhaustion of persistently activated mouse CD4+ T cells. Oncoimmunology. 14:25213922025. View Article : Google Scholar :

118 

Stachowiak M, Becker WJ, Olkhanud PB, Moreno PA, Markowicz S, Berzofsky JA and Sarnowska E: Mechanisms underlying immunosuppression by regulatory cells. Front Immunol. 15:13281932024. View Article : Google Scholar

119 

Mastelic-Gavillet B, Navarro Rodrigo B, Décombaz L, Wang H, Ercolano G, Ahmed R, Lozano LE, Ianaro A, Derré L, Valerio M, et al: Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8+ T cells. J Immunother Cancer. 7:2572019. View Article : Google Scholar :

120 

Sumitomo R, Huang CL, Fujita M, Cho H and Date H: Differential expression of PD-L1 and PD-L2 is associated with the tumor microenvironment of TILs and M2 TAMs and tumor differentiation in non-small cell lung cancer. Oncol Rep. 47:732022. View Article : Google Scholar :

121 

Zhang Y, Zhang Z, Ding Y, Fang Y, Wang P, Chu W, Jin Z, Yang X, Wang J, Lou J and Qian Q: Phase I clinical trial of EGFR-specific CAR-T cells generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer patients. J Cancer Res Clin Oncol. 147:3725–3734. 2021. View Article : Google Scholar : PubMed/NCBI

122 

Sterner RC and Sterner RM: CAR-T cell therapy: Current limitations and potential strategies. Blood Cancer J. 11:692021. View Article : Google Scholar : PubMed/NCBI

123 

Labanieh L and Mackall CL: CAR immune cells: Design principles, resistance and the next generation. Nature. 614:635–648. 2023. View Article : Google Scholar : PubMed/NCBI

124 

Kong Q, Zhu H, Gong W, Deng X, Liu B and Dong J: Modified Bushen Yiqi formula enhances antitumor immunity by reducing the chemotactic recruitment of M2-TAMs and PMN-MDSCs in Lewis lung cancer-bearing mice. J Ethnopharmacol. 319:1171832024. View Article : Google Scholar

125 

Chen C, Hou J, Yu S, Li W, Wang X, Sun H, Qin T, Claret FX, Guo H and Liu Z: Role of cancer-associated fibroblasts in the resistance to antitumor therapy, and their potential therapeutic mechanisms in non-small cell lung cancer. Oncol Lett. 21:4132021. View Article : Google Scholar : PubMed/NCBI

126 

Feng H, Cao B, Peng X and Wei Q: Cancer-associated fibroblasts strengthen cell proliferation and EGFR TKIs resistance through aryl hydrocarbon receptor dependent signals in non-small cell lung cancer. BMC Cancer. 22:7642022. View Article : Google Scholar : PubMed/NCBI

127 

Li F, Zhao S, Cui Y, Guo T, Qiang J, Xie Q, Yu W, Guo W, Deng W, Gu C and Wu T: α1,6-Fucosyltransferase (FUT8) regulates the cancer-promoting capacity of cancer-associated fibroblasts (CAFs) by modifying EGFR core fucosylation (CF) in non-small cell lung cancer (NSCLC). Am J Cancer Res. 10:816–837. 2020.

128 

Yang F, Yan Y, Yang Y, Hong X, Wang M, Yang Z, Liu B and Ye L: MiR-210 in exosomes derived from CAFs promotes non-small cell lung cancer migration and invasion through PTEN/PI3K/AKT pathway. Cell Signal. 73:1096752020. View Article : Google Scholar : PubMed/NCBI

129 

Chen Y, Zhu S, Yang L, Lu Y and Ye X: Cancer-associated fibroblasts (CAFs) regulate lung cancer malignant progression by transferring SERPINE2 (PN1) via exosomes. Curr Mol Med. 25:1025–1037. 2025. View Article : Google Scholar

130 

Sun Y, Ying K, Sun J, Wang Y, Qiu L, Ji M, Sun L and Chen J: PRRX1-OLR1 axis supports CAFs-mediated lung cancer progression and immune suppression. Cancer Cell Int. 24:2472024. View Article : Google Scholar : PubMed/NCBI

131 

Wang H, Wu C, Wan S, Zhang H, Zhou S and Liu G: Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway. Toxicology. 308:104–112. 2013. View Article : Google Scholar : PubMed/NCBI

132 

Wang H, Zhu Y, Zhao M, Wu C, Zhang P, Tang L, Zhang H, Chen X, Yang Y and Liu G: miRNA-29c suppresses lung cancer cell adhesion to extracellular matrix and metastasis by targeting integrin β1 and matrix metalloproteinase2 (MMP2). PLoS One. 8:e701922013. View Article : Google Scholar

133 

Bi HX, Shi HB, Zhang T and Cui G: PRDM14 promotes the migration of human non-small cell lung cancer through extracellular matrix degradation in vitro. Chin Med J (Engl). 128:373–377. 2015. View Article : Google Scholar : PubMed/NCBI

134 

Zhang T, Cui G, Yao YL, Guo Y, Wang QC, Li XN and Feng WM: Inhibition of nonsmall cell lung cancer cell migration by protein arginine methyltransferase 1-small hairpin RNA through inhibiting Epithelial-mesenchymal transition, extracellular matrix degradation, and src phosphorylation in vitro. Chin Med J (Engl). 128:1202–1208. 2015. View Article : Google Scholar : PubMed/NCBI

135 

Wang Y, Zhang T, Guo L, Ren T and Yang Y: Stromal extracellular matrix is a microenvironmental cue promoting resistance to EGFR tyrosine kinase inhibitors in lung cancer cells. Int J Biochem Cell Biol. 106:96–106. 2019. View Article : Google Scholar

136 

Shie WY, Chu PH, Kuo MY, Chen HW, Lin MT, Su XJ, Hong YL and Chou HE: Acidosis promotes the metastatic colonization of lung cancer via remodeling of the extracellular matrix and vasculogenic mimicry. Int J Oncol. 63:1362023. View Article : Google Scholar : PubMed/NCBI

137 

Peláez R, Ochoa R, Pariente A, Villanueva-Martínez Á, Pérez-Sala Á and Larráyoz IM: Sterculic acid alters adhesion molecules expression and extracellular matrix compounds to regulate migration of lung cancer cells. Cancers (Basel). 13:43702021. View Article : Google Scholar : PubMed/NCBI

138 

Abdel-Hafez SM, Gallei M, Wagner S and Schneider M: Inhalable nano-structured microparticles for extracellular matrix modulation as a potential delivery system for lung cancer. Eur J Pharm Biopharm. 204:1145122024. View Article : Google Scholar : PubMed/NCBI

139 

Frezzetti D, Gallo M, Maiello MR, D'Alessio A, Esposito C, Chicchinelli N, Normanno N and De Luca A: VEGF as a potential target in lung cancer. Expert Opin Ther Targets. 21:959–966. 2017. View Article : Google Scholar : PubMed/NCBI

140 

Villaruz LC and Socinski MA: The role of Anti-angiogenesis in non-small-cell lung cancer: An update. Curr Oncol Rep. 17:262015. View Article : Google Scholar : PubMed/NCBI

141 

Socinski MA, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodríguez-Abreu D, Moro-Sibilot D, Thomas CA, et al: IMpower150 final overall survival analyses for atezolizumab plus bevacizumab and chemotherapy in First-line metastatic nonsquamous NSCLC. J Thorac Oncol. 16:1909–1924. 2021. View Article : Google Scholar : PubMed/NCBI

142 

Qiang H, Wang Y, Zhang Y, Li J, Zhang L, Du H, Ling X, Cao S, Zhou Y, Zhong R and Zhong H: Efficacy of first-line chemotherapy combined with immunotherapy or anti-angiogenic therapy in advanced KRAS-mutant non-small cell lung cancer. Transl Oncol. 53:1023172025. View Article : Google Scholar : PubMed/NCBI

143 

Cai Q, Hu K, Dong S, Li X, Hu S, Deng W and Ou W: Tumor cavitation in patients with non-small-cell lung cancer receiving anti-angiogenic therapy with apatinib. Transl Lung Cancer Res. 13:1708–1717. 2024. View Article : Google Scholar : PubMed/NCBI

144 

Zhang X, Sun Q, Chen R, Zhao M, Cai F, Cui Z and Jiang H: Efficacy and safety of combining anti-angiogenic therapy, radiotherapy, and PD-1 inhibitors in patients with driver gene-negative non-small cell lung cancer brain metastases: A retrospective study. BMC Cancer. 24:14922024. View Article : Google Scholar : PubMed/NCBI

145 

Song JQ, Wang X, Zeng ZM, Liang PA, Zhong CY and Liu AW: Efficacy of PD-1 Inhibitors combined with anti-angiogenic therapy in driver gene mutation negative non-small-cell lung cancer with brain metastases. Discov Med. 35:321–331. 2023. View Article : Google Scholar : PubMed/NCBI

146 

Itatani Y, Kawada K, Yamamoto T and Sakai Y: Resistance to Anti-angiogenic therapy in Cancer-alterations to Anti-VEGF pathway. Int J Mol Sci. 19:12322018. View Article : Google Scholar : PubMed/NCBI

147 

Bergers G and Hanahan D: Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 8:592–603. 2008. View Article : Google Scholar : PubMed/NCBI

148 

Wu Y, Yan Y, Guo Y, Niu M, Zhou B, Zhang J, Zhou P, Chu Q, Mei Q, Yi M and Wu K: Anti-TGF-β/PD-L1 bispecific antibody synergizes with radiotherapy to enhance antitumor immunity and mitigate radiation-induced pulmonary fibrosis. J Hematol Oncol. 18:242025. View Article : Google Scholar

149 

Huehls AM, Coupet TA and Sentman CL: Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol. 93:290–296. 2015. View Article : Google Scholar

150 

Si Y, Pei X, Wang X, Han Q, Xu C and Zhang B: An Anti-EGFR/anti-HER2 bispecific antibody with enhanced antitumor activity against acquired Gefitinib-resistant NSCLC cells. Protein Pept Lett. 28:1290–1297. 2021. View Article : Google Scholar

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Spandidos Publications style
Liu L, Yang L, Li H, Shang T and Liu L: The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review). Int J Oncol 68: 11, 2026.
APA
Liu, L., Yang, L., Li, H., Shang, T., & Liu, L. (2026). The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review). International Journal of Oncology, 68, 11. https://doi.org/10.3892/ijo.2025.5824
MLA
Liu, L., Yang, L., Li, H., Shang, T., Liu, L."The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review)". International Journal of Oncology 68.1 (2026): 11.
Chicago
Liu, L., Yang, L., Li, H., Shang, T., Liu, L."The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review)". International Journal of Oncology 68, no. 1 (2026): 11. https://doi.org/10.3892/ijo.2025.5824
Copy and paste a formatted citation
x
Spandidos Publications style
Liu L, Yang L, Li H, Shang T and Liu L: The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review). Int J Oncol 68: 11, 2026.
APA
Liu, L., Yang, L., Li, H., Shang, T., & Liu, L. (2026). The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review). International Journal of Oncology, 68, 11. https://doi.org/10.3892/ijo.2025.5824
MLA
Liu, L., Yang, L., Li, H., Shang, T., Liu, L."The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review)". International Journal of Oncology 68.1 (2026): 11.
Chicago
Liu, L., Yang, L., Li, H., Shang, T., Liu, L."The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review)". International Journal of Oncology 68, no. 1 (2026): 11. https://doi.org/10.3892/ijo.2025.5824
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