Progress of immune checkpoint LAG‑3 in immunotherapy (Review)
- Authors:
- Chanchan Shan
- Xing Li
- Jian Zhang
-
Affiliations: Department of Cardiology, Wuxi No. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu 214000, P.R. China, Department of Orthopaedic Surgery, Wuxi No. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu 214000, P.R. China - Published online on: September 8, 2020 https://doi.org/10.3892/ol.2020.12070
- Article Number: 207
This article is mentioned in:
Abstract
 |
|
Galluzzi L, Vacchelli E, Bravo-San Pedro JM, Buqué A, Senovilla L, Baracco EE, Bloy N, Castoldi F, Abastado JP, Agostinis P, et al: Classification of current anticancer immunotherapies. Oncotarget. 5:12472–12508. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Li X, Shao C, Shi Y and Han W: Lessons learned from the blockade of immune checkpoints in cancer immunotherapy. J Hematol Oncol. 11:312018. View Article : Google Scholar : PubMed/NCBI | |
|
Fang Z, Han H and Liang L: Progression in chimeric antigen receptor T (CAR-T) cell therapy of solid tumors: A review. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 35:944–948. 2019.(In Chinese). PubMed/NCBI | |
|
Krishnamurthy A and Jimeno A: Bispecific antibodies for cancer therapy: A review. Pharmacol Ther. 185:122–134. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Sadreddini S, Baradaran B, Aghebati-Maleki A, Sadreddini S, Shanehbandi D, Fotouhi A and Aghebati-Maleki L: Immune checkpoint blockade opens a new way to cancer immunotherapy. J Cell Physiol. 234:8541–8549. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao Y, Yang W, Huang Y, Cui R, Li X and Li B: Evolving roles for targeting CTLA-4 in cancer immunotherapy. Cell Physiol Biochem. 47:721–734. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Weinmann SC and Pisetsky DS: Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors. Rheumatology (Oxford). 58 (Suppl 7):vii59–vii67. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Postow MA, Callahan MK and Wolchok JD: Immune checkpoint blockade in cancer therapy. J Clin Oncol. 33:1974–1982. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Shergold AL, Millar R and Nibbs RJB: Understanding and overcoming the resistance of cancer to PD-1/PD-L1 blockade. Pharmacol Res. 145:1042582019. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Yuan R, Song W, Sun J, Liu D and Li Z: PD-1, PD-L1 (B7-H1) and tumor-site immune modulation therapy: The historical perspective. J Hematol Oncol. 10:342017. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao X and Subramanian S: Intrinsic resistance of solid tumors to immune checkpoint blockade therapy. Cancer Res. 77:817–822. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Burugu S, Gao D, Leung S, Chia SK and Nielsen TO: LAG-3+ tumor infiltrating lymphocytes in breast cancer: Clinical correlates and association with PD-1/PD-L1+ tumors. Ann Oncol. 28:2977–2984. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E and Hercend T: LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med. 171:1393–1405. 1990. View Article : Google Scholar : PubMed/NCBI | |
|
Huard B, Prigent P, Tournier M, Bruniquel D and Triebel F: CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins. Eur J Immunol. 25:2718–2721. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Dijkstra JM, Somamoto T, Moore L, Hordvik I, Ototake M and Fischer U: Identification and characterization of a second CD4-like gene in teleost fish. Mol Immunol. 43:410–419. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Sierro S, Romero P and Speiser DE: The CD4-like molecule LAG-3, biology and therapeutic applications. Expert Opin Ther Targets. 15:91–101. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Workman CJ, Dugger KJ and Vignali DA: Cutting edge: Molecular analysis of the negative regulatory function of lymphocyte activation gene-3. J Immunol. 169:5392–5395. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Goldberg MV and Drake CG: LAG-3 in cancer immunotherapy. Curr Top Microbiol Immunol. 344:269–278. 2011.PubMed/NCBI | |
|
Iouzalen N, Andreae S, Hannier S and Triebel F: LAP, a lymphocyte activation gene-3 (LAG-3)-associated protein that binds to a repeated EP motif in the intracellular region of LAG-3, may participate in the down-regulation of the CD3/TCR activation pathway. Eur J Immunol. 31:2885–2891. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Li N, Wang Y, Forbes K, Vignali KM, Heale BS, Saftig P, Hartmann D, Black RA, Rossi JJ, Blobel CP, et al: Metalloproteases regulate T-cell proliferation and effector function via LAG-3. EMBO J. 26:494–504. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Demeure CE, Wolfers J, Martin-Garcia N, Gaulard P and Triebel F: T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): Role of LAG-3/MHC class II interactions in cell-cell contacts. Eur J Cancer. 37:1709–1718. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Huard B, Mastrangeli R, Prigent P, Bruniquel D, Donini S, El-Tayar N, Maigret B, Dréano M and Triebel F: Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc Natl Acad Sci USA. 94:5744–5749. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Kouo T, Huang L, Pucsek AB, Cao M, Solt S, Armstrong T and Jaffee E: Galectin-3 shapes antitumor immune responses by suppressing CD8+ T cells via LAG-3 and inhibiting expansion of plasmacytoid dendritic cells. Cancer Immunol Res. 3:412–423. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
O'Driscoll L, Linehan R, Liang YH, Joyce H, Oglesby I and Clynes M: Galectin-3 expression alters adhesion, motility and invasion in a lung cell line (DLKP), in vitro. Anticancer Res. 22:3117–3125. 2002.PubMed/NCBI | |
|
Califice S, Castronovo V, Bracke M and van den Brûle F: Dual activities of galectin-3 in human prostate cancer: Tumor suppression of nuclear galectin-3 vs. tumor promotion of cytoplasmic galectin-3. Oncogene. 23:7527–7536. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Wang C, Zhou X, Ma L, Zhuang Y, Wei Y, Zhang L, Jin S, Liang W, Shen X, Li C, et al: Galectin-3 may serve as a marker for poor prognosis in colorectal cancer: A meta-analysis. Pathol Res Pract. 215:1526122019. View Article : Google Scholar : PubMed/NCBI | |
|
Boutas I, Potiris A, Brenner W, Lebrecht A, Hasenburg A, Kalantaridou S and Schmidt M: The expression of galectin-3 in breast cancer and its association with chemoresistance: A systematic review of the literature. Arch Gynecol Obstet. 300:1113–1120. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Dumic J, Dabelic S and Flogel M: Galectin-3: An open-ended story. Biochim Biophys Acta. 1760:616–635. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Xu F, Liu J, Liu D, Liu B, Wang M, Hu Z, Du X, Tang L and He F: LSECtin expressed on melanoma cells promotes tumor progression by inhibiting antitumor T-cell responses. Cancer Res. 74:3418–3428. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Yang J, Wang H, Wang M, Liu B, Xu H, Xu F, Zhao D, Hu B, Zhao N, Wang J, et al: Involvement of LSECtin in the hepatic natural killer cell response. Biochem Biophys Res Commun. 476:49–55. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Mao X, Ou MT, Karuppagounder SS, Kam TI, Yin X, Xiong Y, Ge P, Umanah GE, Brahmachari S, Shin JH, et al: Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science. 353:aah33742016. View Article : Google Scholar : PubMed/NCBI | |
|
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 e312. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Visan I: New ligand for LAG-3. Nat Immunol. 20:1112019. View Article : Google Scholar | |
|
Durham NM, Nirschl CJ, Jackson CM, et al: Lymphocyte activation gene 3 (LAG-3) modulates the ability of CD4 T-cells to be suppressed in vivo. PLoS One. 9:e1090802014. View Article : Google Scholar : PubMed/NCBI | |
|
Pena J, Jones NG, Bousheri S, Bangsberg DR and Cao H: Lymphocyte activation gene-3 expression defines a discrete subset of HIV-specific CD8+ T cells that is associated with lower viral load. AIDS Res Hum Retroviruses. 30:535–541. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, et al: Role of LAG-3 in regulatory T cells. Immunity. 21:503–513. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Huard B, Tournier M and Triebel F: LAG-3 does not define a specific mode of natural killing in human. Immunol Lett. 61:109–112. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Kisielow M, Kisielow J, Capoferri-Sollami G and Karjalainen K: Expression of lymphocyte activation gene 3 (LAG-3) on B cells is induced by T cells. Eur J Immunol. 35:2081–2088. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Workman CJ, Wang Y, El Kasmi KC, Pardoll DM, Murray PJ, Drake CG and Vignali DA: LAG-3 regulates plasmacytoid dendritic cell homeostasis. J Immunol. 182:1885–1891. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, Subramaniam S, Blattman JN, Barber DL and Ahmed R: Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 27:670–684. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Fourcade J, Sun Z, Pagliano O, Guillaume P, Luescher IF, Sander C, Kirkwood JM, Olive D, Kuchroo V and Zarour HM: CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1. Cancer Res. 72:887–896. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Brown KE, Freeman GJ, Wherry EJ and Sharpe AH: Role of PD-1 in regulating acute infections. Curr Opin Immunol. 22:397–401. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Vieyra-Lobato MR, Vela-Ojeda J, Montiel-Cervantes L, Lopez-Santiago R and Moreno-Lafont MC: Description of CD8(+) regulatory T lymphocytes and their specific intervention in graft-versus-host and infectious diseases, autoimmunity, and cancer. J Immunol Res. 2018:37587132018. View Article : Google Scholar : PubMed/NCBI | |
|
Haanen JB, Thienen H and Blank CU: Toxicity patterns with immunomodulating antibodies and their combinations. Semi Oncol. 42:423–428. 2015. View Article : Google Scholar | |
|
Pardoll DM: The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 12:252–264. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Huard B, Tournier M, Hercend T, Triebel F and Faure F: Lymphocyte-activation gene 3/major histocompatibility complex class II interaction modulates the antigenic response of CD4+ T lymphocytes. Eur J Immunol. 24:3216–3221. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Joller N and Kuchroo VK: Tim-3, Lag-3, and TIGIT. Curr Top Microbiol Immunol. 410:127–156. 2017.PubMed/NCBI | |
|
Grosso JF, Kelleher CC, Harris TJ, Maris CH, Hipkiss EL, De Marzo A, Anders R, Netto G, Getnet D, Bruno TC, et al: LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest. 117:3383–3392. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Workman CJ and Vignali DA: Negative regulation of T cell homeostasis by lymphocyte activation gene-3 (CD223). J Immunol. 174:688–695. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Baitsch L, Legat A, Barba L, Fuertes Marraco SA, Rivals JP, Baumgaertner P, Christiansen-Jucht C, Bouzourene H, Rimoldi D, Pircher H, et al: Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization. PLoS One. 7:e308522012. View Article : Google Scholar : PubMed/NCBI | |
|
Baitsch L, Baumgaertner P, Devêvre E, Raghav SK, Legat A, Barba L, Wieckowski S, Bouzourene H, Deplancke B, Romero P, et al: Exhaustion of tumor-specific CD8(+) T cells in metastases from melanoma patients. J Clin Invest. 121:2350–2360. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
McLane LM, Abdel-Hakeem MS and Wherry EJ: CD8 T cell exhaustion during chronic viral infection and cancer. Annu Rev Immunol. 37:457–495. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Andrews LP, Marciscano AE, Drake CG and Vignali DA: LAG3 (CD223) as a cancer immunotherapy target. Immunol Rev. 276:80–96. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
He Y, Rivard CJ, Rozeboom L, Yu H, Ellison K, Kowalewski A, Zhou C and Hirsch FR: Lymphocyte-activation gene-3, an important immune checkpoint in cancer. Cancer Sci. 107:1193–1197. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL, et al: Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 72:917–927. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Casati C, Camisaschi C, Rini F, Arienti F, Rivoltini L, Triebel F, Parmiani G and Castelli C: Soluble human LAG-3 molecule amplifies the in vitro generation of type 1 tumor-specific immunity. Cancer Res. 66:4450–4460. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Bettini M, Szymczak-Workman AL, Forbes K, Castellaw AH, Selby M, Pan X, Drake CG, Korman AJ and Vignali DA: Cutting edge: Accelerated autoimmune diabetes in the absence of LAG-3. J Immunol. 187:3493–3498. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Burugu S, Dancsok AR and Nielsen TO: Emerging targets in cancer immunotherapy. Semin Cancer Biol. 52:39–52. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kuchroo VK, Anderson AC and Petrovas C: Coinhibitory receptors and CD8 T cell exhaustion in chronic infections. Curr Opin HIV AIDS. 9:439–445. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Hannier S and Triebel F: The MHC class II ligand lymphocyte activation gene-3 is co-distributed with CD8 and CD3-TCR molecules after their engagement by mAb or peptide-MHC class I complexes. Int Immunol. 11:1745–1752. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Triebel F: LAG-3: A regulator of T-cell and DC responses and its use in therapeutic vaccination. Trends Immunol. 24:619–622. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Villadolid J and Amin A: Immune checkpoint inhibitors in clinical practice: Update on management of immune-related toxicities. Transl Lung Cancer Res. 4:560–575. 2015.PubMed/NCBI | |
|
Sharma P and Allison JP: The future of immune checkpoint therapy. Science. 348:56–61. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou G, Sprengers D, Boor PPC, Doukas M, Schutz H, Mancham S, Pedroza-Gonzalez A, Polak WG, de Jonge J, Gaspersz M, et al: Antibodies against immune checkpoint molecules restore functions of tumor-infiltrating T cells in hepatocellular carcinomas. Gastroenterology. 153:1107–1119.e10. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
He Y, Yu H, Rozeboom L, Rivard CJ, Ellison K, Dziadziuszko R, Suda K, Ren S, Wu C, Hou L, et al: LAG-3 protein expression in non-small cell lung cancer and its relationship with PD-1/PD-L1 and tumor-infiltrating lymphocytes. J Thorac Oncol. 12:814–823. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Matsuzaki J, Gnjatic S, Mhawech-Fauceglia P, Beck A, Miller A, Tsuji T, Eppolito C, Qian F, Lele S, Shrikant P, Old LJ and Odunsi K: Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci USA. 107:7875–7880. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Ma QY, Huang DY, Zhang HJ, Wang S and Chen XF: Function and regulation of LAG3 on CD4+CD25− T cells in non-small cell lung cancer. Exp Cell Res. 360:358–364. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Hald SM, Rakaee M, Martinez I, Richardsen E, Al-Saad S, Paulsen EE, Blix ES, Kilvaer T, Andersen S, Busund LT, et al: LAG-3 in non-small-cell lung cancer: expression in primary tumors and metastatic lymph nodes is associated with improved survival. Clin Lung Cancer. 19:249–259.e2. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Li FJ, Zhang Y, Jin GX, Yao L and Wu DQ: Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8(+) T cell in HCC patients. Immunol Lett. 150:116–122. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Camisaschi C, Casati C, Rini F, Perego M, De Filippo A, Triebel F, Parmiani G, Belli F, Rivoltini L and Castelli C: LAG-3 expression defines a subset of CD4(+)CD25(high)Foxp3(+) regulatory T cells that are expanded at tumor sites. J Immunol. 184:6545–6551. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Chen J and Chen Z: The effect of immune microenvironment on the progression and prognosis of colorectal cancer. Med Oncol. 31:822014. View Article : Google Scholar : PubMed/NCBI | |
|
Gagliani N, Magnani CF, Huber S, Gianolini ME, Pala M, Licona-Limon P, Guo B, Herbert DR, Bulfone A, Trentini F, et al: Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med. 19:739–746. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Chen BJ, Dashnamoorthy R, Galera P, Makarenko V, Chang H, Ghosh S and Evens AM: The immune checkpoint molecules PD-1, PD-L1, TIM-3 and LAG-3 in diffuse large B-cell lymphoma. Oncotarget. 10:2030–2040. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Wierz M, Pierson S, Guyonnet L, Viry E, Lequeux A, Oudin A, Niclou SP, Ollert M, Berchem G, Janji B, et al: Dual PD1/LAG3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia. Blood. 131:1617–1621. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Huang RY, Eppolito C, Lele S, Shrikant P, Matsuzaki J and Odunsi K: LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model. Oncotarget. 6:27359–27377. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Baumeister SH, Freeman GJ, Dranoff G and Sharpe AH: Coinhibitory pathways in immunotherapy for cancer. Annu Rev Immunol. 34:539–573. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Li B, Chan HL and Chen P: Immune checkpoint inhibitors: Basics and challenges. Curr Med Chem. 26:3009–3025. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Akinleye A and Rasool Z: Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol. 12:922019. View Article : Google Scholar : PubMed/NCBI | |
|
Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, Blosser RL, Fan H, Wang H, Luber BS, et al: The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 5:43–51. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Vilgelm AE, Johnson DB and Richmond A: Combinatorial approach to cancer immunotherapy: Strength in numbers. J Leukoc Biol. 100:275–290. 2016. View Article : Google Scholar : PubMed/NCBI |
