Recent Developments in Immunotherapy for Gastrointestinal Tract Cancers

Overview

Journal J Hematol Oncol

Publisher Biomed Central

Specialties Hematology
Oncology

Date 2024 Aug 9

PMID 39123202

Authors

Xiaoyi Chong

Yelizhati Madeti

Jieyuan Cai

Wenfei Li

Lin Cong

Jialin Lu

Liyang Mo

Huizhen Liu

Siyi He

Chao Yu

Zhiruo Zhou

Boya Wang

Yanshuo Cao

Zhenghang Wang

Lin Shen

Yakun Wang

Xiaotian Zhang

Affiliations

Soon will be listed here.

Abstract

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. The role of immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in the treatment of advanced and perioperative GI tract cancers. Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen for unselected advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), and advanced esophageal cancer (EC). In addition, the encouraging performance of claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy in later-line GI tract cancers brings new hope for cell therapy in solid tumour treatment. Nevertheless, immunotherapy for GI tumour remains yet precise, and researchers are dedicated to further maximising and optimising the efficacy. This review summarises the important research, latest progress, and future directions of immunotherapy for GI tract cancers including EC, G/GEJC, and CRC.

Citing Articles

Exploring the therapeutic potential of "Zhi-Zhen" formula for oxaliplatin resistance in colorectal cancer: an integrated study combining UPLC-QTOF-MS/MS, bioinformatics, network pharmacology, and experimental validation.

Li Y, Chen K, Li Q, Liu Q, Han H, Liu H Front Med (Lausanne). 2025; 12:1516307.

PMID: 40078400 PMC: 11897289. DOI: 10.3389/fmed.2025.1516307.

A High-Resolution Digital Pathological Image Staining Style Transfer Model Based on Gradient Guidance.

Tang Y, Zhou Y, Zhang S, Lu Y Bioengineering (Basel). 2025; 12(2).

PMID: 40001706 PMC: 11851416. DOI: 10.3390/bioengineering12020187.

(Somm. et Levier) Manden.-A Comprehensive Phytochemical and Biological Evaluation.

Nersezashvili M, Berashvili D, Jokhadze M, Metreveli M, Swiatek L, Salwa K Molecules. 2025; 30(3).

PMID: 39942828 PMC: 11820956. DOI: 10.3390/molecules30030725.

FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects.

Wang W, Liu X, Zhao L, Jiang K, Yu Z, Yang R Front Pharmacol. 2025; 15:1505027.

PMID: 39749199 PMC: 11694028. DOI: 10.3389/fphar.2024.1505027.

Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.

Wei J, Li W, Zhang P, Guo F, Liu M Mol Cancer. 2024; 23(1):279.

PMID: 39725966 PMC: 11670468. DOI: 10.1186/s12943-024-02179-5.

References

Fukumura D, Kloepper J, Amoozgar Z, Duda D, Jain R . Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol. 2018; 15(5):325-340. PMC: 5921900. DOI: 10.1038/nrclinonc.2018.29. View

Wu K, Lin K, Li X, Yuan X, Xu P, Ni P . Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment. Front Immunol. 2020; 11:1731. PMC: 7417513. DOI: 10.3389/fimmu.2020.01731. View

Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M . Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007; 109(9):3812-9. DOI: 10.1182/blood-2006-07-035972. View

Wu Z, Zhang Y, Cheng Y, Li J, Li F, Wang C . PD-1 blockade plus COX inhibitors in dMMR metastatic colorectal cancer: Clinical, genomic, and immunologic analyses from the PCOX trial. Med. 2024; 5(8):998-1015.e6. DOI: 10.1016/j.medj.2024.05.002. View

Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G . The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2014; 26(2):259-71. PMC: 6267863. DOI: 10.1093/annonc/mdu450. View

Ni W, Mo H, Liu Y, Xu Y, Qin C, Zhou Y . Targeting cholesterol biosynthesis promotes anti-tumor immunity by inhibiting long noncoding RNA SNHG29-mediated YAP activation. Mol Ther. 2021; 29(10):2995-3010. PMC: 8530930. DOI: 10.1016/j.ymthe.2021.05.012. View

Kloor M, Michel S, Buckowitz B, Ruschoff J, Buttner R, Holinski-Feder E . Beta2-microglobulin mutations in microsatellite unstable colorectal tumors. Int J Cancer. 2007; 121(2):454-8. DOI: 10.1002/ijc.22691. View

Galluzzi L, Humeau J, Buque A, Zitvogel L, Kroemer G . Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol. 2020; 17(12):725-741. DOI: 10.1038/s41571-020-0413-z. View

Zang X, Sullivan P, Soslow R, Waitz R, Reuter V, Wilton A . Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas. Mod Pathol. 2010; 23(8):1104-12. PMC: 2976590. DOI: 10.1038/modpathol.2010.95. View

10.

Bang Y, Van Cutsem E, Feyereislova A, Chung H, Shen L, Sawaki A . Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376(9742):687-97. DOI: 10.1016/S0140-6736(10)61121-X. View

11.

Hu J, Zhang L, Xia H, Yan Y, Zhu X, Sun F . Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing. Genome Med. 2023; 15(1):14. PMC: 9985263. DOI: 10.1186/s13073-023-01164-9. View

12.

Chang C, Qiu J, OSullivan D, Buck M, Noguchi T, Curtis J . Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell. 2015; 162(6):1229-41. PMC: 4864363. DOI: 10.1016/j.cell.2015.08.016. View

13.

Kwon M, Kim G, Kim R, Kim K, Kim S, Smith S . Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer. J Immunother Cancer. 2022; 10(7). PMC: 9258491. DOI: 10.1136/jitc-2022-005041. View

14.

Qiu M, Wang C, Wu Z, Zhao Q, Zhao Z, Huang C . Dynamic single-cell mapping unveils Epstein‒Barr virus-imprinted T-cell exhaustion and on-treatment response. Signal Transduct Target Ther. 2023; 8(1):370. PMC: 10514267. DOI: 10.1038/s41392-023-01622-1. View

15.

Cheng B, Tong G, Wu X, Cai W, Li Z, Tong Z . Enumeration And Characterization Of Circulating Tumor Cells And Its Application In Advanced Gastric Cancer. Onco Targets Ther. 2019; 12:7887-7896. PMC: 6768312. DOI: 10.2147/OTT.S223222. View

16.

Dong X, Fan J, Xie W, Wu X, Wei J, He Z . Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer. Br J Cancer. 2023; 129(3):551-562. PMC: 10403530. DOI: 10.1038/s41416-023-02319-6. View

17.

Fakih M, Sandhu J, Lim D, Li X, Li S, Wang C . Regorafenib, Ipilimumab, and Nivolumab for Patients With Microsatellite Stable Colorectal Cancer and Disease Progression With Prior Chemotherapy: A Phase 1 Nonrandomized Clinical Trial. JAMA Oncol. 2023; 9(5):627-634. PMC: 9999273. DOI: 10.1001/jamaoncol.2022.7845. View

18.

Morano F, Raimondi A, Pagani F, Lonardi S, Salvatore L, Cremolini C . Temozolomide Followed by Combination With Low-Dose Ipilimumab and Nivolumab in Patients With Microsatellite-Stable, O-Methylguanine-DNA Methyltransferase-Silenced Metastatic Colorectal Cancer: The MAYA Trial. J Clin Oncol. 2022; 40(14):1562-1573. PMC: 9084437. DOI: 10.1200/JCO.21.02583. View

19.

Kelly R, Landon B, Zaidi A, Singh D, Canzoniero J, Balan A . Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses. Nat Med. 2024; 30(4):1023-1034. PMC: 11031406. DOI: 10.1038/s41591-024-02877-z. View

20.

Yu P, Fu Y . Tumor-infiltrating T lymphocytes: friends or foes?. Lab Invest. 2006; 86(3):231-45. DOI: 10.1038/labinvest.3700389. View