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Review Open Access

Progress in perioperative immunotherapy for lung cancer and analysis of therapy (Review)

  • Authors:
    • Xiao Ma
    • Gaofeng Li
    • Heng Li
    • Lanjun Li
    • Hanting Zhao
    • Zhiqing Liu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery II, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650106, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 100
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    Published online on: January 9, 2026
       https://doi.org/10.3892/ol.2026.15453
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Abstract

Surgical treatment has long been the preferred approach for lung cancer. In recent years, postoperative adjuvant immunotherapy following surgical treatment has demonstrated good efficacy. Building on this foundation, the introduction of neoadjuvant immunotherapy prior to surgery has also reported promising results in a number of clinical trials. The aim of the present review was to summarize recent research findings associated with perioperative immunotherapy for lung cancer, including key outcomes from both neoadjuvant and adjuvant therapies. The discussion of the results of the present review primarily addressed efficacy, safety, survival data and programmed death‑ligand 1 subgroup analyses. Furthermore, the advantages and limitations of different treatment modalities, including monotherapies and combination therapies, were discussed. Furthermore, the present review incorporated discussions on the applicability of biomarkers in perioperative immunotherapy, the role of immunotherapy combined with other treatments during the perioperative period, mechanisms of resistance and potential solutions to these challenges. In conclusion, the present review offers a systematic examination of the theoretical foundations of perioperative immunotherapy for lung cancer, simultaneously presenting key clinical evidence (including neoadjuvant therapy, adjuvant therapy and ‘sandwich’ combination regimens), diverse combination strategies (chemotherapy and radiotherapy), the current status of biomarker applications and challenges in underlying drug resistance mechanisms for perioperative immunotherapy. It proposes a dynamic monitoring model and clinical decision pathway for omission of adjuvant immunotherapy in non‑small cell lung cancer. Lastly, based upon the latest evidence‑based medical research, the present review aims to provide clinicians and researchers with comprehensive decision‑making references and scientific guidance.

View Figures

Figure 1

Mechanism of tumor immune cycle. 1)
When tumor cells die, they release tumor antigens, which are then
captured by DCs in the lymph nodes. 2) Antigen presentation, where
dendritic cells process and present tumor antigens to naïve T
cells. 3) Priming and activation of naïve T cells: The naïve T
cells receive an antigenic signal (from dendritic cells) and a
co-stimulatory signal (e.g., CD28/B7), subsequently differentiating
into effector T cells. 4) After CD40L on the T-cell surface binds
to CD40 on the DC surface, this ‘reverse signaling’ potently acts
back upon the DC. This further upregulates the expression of
co-stimulatory molecules such as B7 on the dendritic cell, thereby
establishing a positive feedback loop for T cell activation. 5)
Migration of activated T cells: Effector T cells exit the lymph
node, enter the bloodstream and traffic towards the tumor site
guided by chemokine signals. 6) Under the influence of chemokines,
T cells first undergo firm adhesion to the vascular endothelium.
They then deform and transmigrate through the junctions between
endothelial cells to enter the tumor immune microenvironment. 7)
Process of T-cell recognition of tumor cells, wherein effector T
cells identify tumor-specific antigens presented on the major
histocompatibility complex molecules of the tumor cells through
their T cell receptors. 8) Cytotoxic killing of tumor cells by T
cells. Effector T cells induce cancer cell apoptosis either by
secreting cytotoxic mediators like perforin and granzymes, or by
activating the death receptor pathway such as Fas/FasL. 9) Lysis of
tumor cells that underwent apoptosis and the subsequent release of
new tumor antigens, indicating the initiation of a renewed
antitumor immunity cycle. 10) Surgery can lead to the formation of
an immunosuppressive microenvironment. The physical tissue damage
from surgical incision causes the release of Damage-Associated
Molecular Patterns (DAMPs); these signals recruit Tregs to the
surgical site and, in some cases, drive the conversion of naïve
CD4+ T cells into newly induced Tregs. This process establishes a
state of local immunosuppression that impedes the antitumor
immunity cycle. 11) Mechanism by which immunotherapy reverses
immune suppression. The co-inhibitory signaling pathway formed by
PD-1 and its primary ligand PD-L1 (B7-H1) impairs the proliferation
and cytokine production of effector T cells. PD-1 inhibitors
(anti-PD-1 antibodies) bind with high affinity to the PD-1 receptor
on T cells, whereas PD-L1 inhibitors (anti-PD-L1 antibodies) bind
to the PD-L1 ligand on tumor cells. This intervention physically
blocks the PD-1/PD-L1 interaction and subsequent downstream
signaling activation. Consequently, the co-stimulatory signals
received by T cells are fully transmitted and TCR signal
transduction is restored to normal. 12) Immunotherapy, primarily
utilizing PD-1/PD-L1 inhibitors, reverses the localized
immunosuppression previously caused by surgery. This enables T
cells to resume their cytotoxic function against tumor cells via
the cancer-immunity cycle, underscoring the critical importance of
perioperative immunotherapy in lung cancer. 13) Immune evasion by
tumor cells, whereby they avoid immune attack through various
immunosuppressive mechanisms (such as PD-L1 overexpression and
infiltration of regulatory T cells) or via antigen loss. 14)
Proliferative phase following tumor immune escape. Specifically,
PD-L1 on tumor cells binds to PD-1 on T cells, delivering an
inhibitory signal. This fosters an immunosuppressive
microenvironment that microenvironment that allows tumor cells to
evade T cell-mediated killing, leading to their uncontrolled
expansion uncontrolled expansion. PD-1, programmed cell death
protein-1; PD-L1, programmed death ligand 1; DC, dendritic cell;
Treg, regulatory T cell.

Figure 2

Clinical decision pathway for
omission of adjuvant immunotherapy in NSCLC. NSCLC, non-small cell
lung cancer; pCR, Pathological complete response; ctDNA,
circulating tumor DNA; EGFR, epidermal growth factor receptor; ALK,
anaplastic lymphoma kinase.

Figure 3

Mechanism of tumor immune resistance.
TCR, T cell receptor; TAM, tumor-associated macrophages; Treg,
regulatory T cells; MDSC, myeloid-derived suppressor cells; PD-L1,
programmed death ligand 1; PD-1, programmed cell death protein-1;
LAG-3, lymphocyte-activation gene 3; TIM-3, T-cell immunoglobulin
and mucin-domain containing-3; MHC-I, major histocompatibility
complex class I; IL-10, interleukin-10; TGF-β, transforming growth
factor-β; CCL4, C-C motif chemokine ligand 4.
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Spandidos Publications style
Ma X, Li G, Li H, Li L, Zhao H and Liu Z: <p>Progress in perioperative immunotherapy for lung cancer and analysis of therapy (Review)</p>. Oncol Lett 31: 100, 2026.
APA
Ma, X., Li, G., Li, H., Li, L., Zhao, H., & Liu, Z. (2026). <p>Progress in perioperative immunotherapy for lung cancer and analysis of therapy (Review)</p>. Oncology Letters, 31, 100. https://doi.org/10.3892/ol.2026.15453
MLA
Ma, X., Li, G., Li, H., Li, L., Zhao, H., Liu, Z."<p>Progress in perioperative immunotherapy for lung cancer and analysis of therapy (Review)</p>". Oncology Letters 31.3 (2026): 100.
Chicago
Ma, X., Li, G., Li, H., Li, L., Zhao, H., Liu, Z."<p>Progress in perioperative immunotherapy for lung cancer and analysis of therapy (Review)</p>". Oncology Letters 31, no. 3 (2026): 100. https://doi.org/10.3892/ol.2026.15453
Copy and paste a formatted citation
x
Spandidos Publications style
Ma X, Li G, Li H, Li L, Zhao H and Liu Z: <p>Progress in perioperative immunotherapy for lung cancer and analysis of therapy (Review)</p>. Oncol Lett 31: 100, 2026.
APA
Ma, X., Li, G., Li, H., Li, L., Zhao, H., & Liu, Z. (2026). <p>Progress in perioperative immunotherapy for lung cancer and analysis of therapy (Review)</p>. Oncology Letters, 31, 100. https://doi.org/10.3892/ol.2026.15453
MLA
Ma, X., Li, G., Li, H., Li, L., Zhao, H., Liu, Z."<p>Progress in perioperative immunotherapy for lung cancer and analysis of therapy (Review)</p>". Oncology Letters 31.3 (2026): 100.
Chicago
Ma, X., Li, G., Li, H., Li, L., Zhao, H., Liu, Z."<p>Progress in perioperative immunotherapy for lung cancer and analysis of therapy (Review)</p>". Oncology Letters 31, no. 3 (2026): 100. https://doi.org/10.3892/ol.2026.15453
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