New Insight in Immunotherapy and Combine Therapy in Colorectal Cancer

Overview

Journal Front Cell Dev Biol

Date 2025 Jan 22

PMID 39839672

Authors

Kai Ji

Hang Jia

Zixuan Liu

Guanyu Yu

Rongbo Wen

Tianshuai Zhang

Zhiying Peng

Wenjiang Man

Yucheng Tian

Can Wang

Qianlong Ling

Wei Zhang

Leqi Zhou

Mulin Liu

Bing Zhu

Affiliations

Soon will be listed here.

Abstract

The advent of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) treatment marks a major breakthrough. These therapies have proven safer and more effective than traditional radiotherapy and targeted treatments. Immunotherapies like pembrolizumab, nivolumab, and ipilimumab have pioneered new treatment avenues, potentially improving patient outcomes and quality of life. Additionally, advances in immunotherapy have prompted detailed research into CRC therapies, especially those integrating ICIs with conventional treatments, providing new hope for patients and shaping future research and practice. This review delves into the mechanisms of various ICIs and evaluates their therapeutic potential when combined with radiotherapy, chemotherapy, and targeted therapies in clinical settings. It also sheds light on the current application and research involving ICIs in CRC treatment.

Citing Articles

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PMID: 39998678 PMC: 11861783. DOI: 10.1007/s00262-025-03973-w.

References

Tawbi H, Schadendorf D, Lipson E, Ascierto P, Matamala L, Castillo Gutierrez E . Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022; 386(1):24-34. PMC: 9844513. DOI: 10.1056/NEJMoa2109970. View

Klempner S, Fabrizio D, Bane S, Reinhart M, Peoples T, Ali S . Tumor Mutational Burden as a Predictive Biomarker for Response to Immune Checkpoint Inhibitors: A Review of Current Evidence. Oncologist. 2019; 25(1):e147-e159. PMC: 6964127. DOI: 10.1634/theoncologist.2019-0244. View

Patel R, Hernandez R, Carlson P, Grudzinski J, Bates A, Jagodinsky J . Low-dose targeted radionuclide therapy renders immunologically cold tumors responsive to immune checkpoint blockade. Sci Transl Med. 2021; 13(602). PMC: 8449934. DOI: 10.1126/scitranslmed.abb3631. View

Zhang X, Wu T, Cai X, Dong J, Xia C, Zhou Y . Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities. Front Immunol. 2022; 13:795972. PMC: 8968082. DOI: 10.3389/fimmu.2022.795972. 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

Apte R, Chen D, Ferrara N . VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 2019; 176(6):1248-1264. PMC: 6410740. DOI: 10.1016/j.cell.2019.01.021. View

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

Meltzer S, Negard A, Bakke K, Hamre H, Kersten C, Hofsli E . Early radiologic signal of responsiveness to immune checkpoint blockade in microsatellite-stable/mismatch repair-proficient metastatic colorectal cancer. Br J Cancer. 2022; 127(12):2227-2233. PMC: 9726864. DOI: 10.1038/s41416-022-02004-0. View

Huang Y, Zhu C, Kondo Y, Anderson A, Gandhi A, Russell A . CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature. 2014; 517(7534):386-90. PMC: 4297519. DOI: 10.1038/nature13848. View

10.

Banta K, Xu X, Chitre A, Au-Yeung A, Takahashi C, OGorman W . Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8 T cell responses. Immunity. 2022; 55(3):512-526.e9. PMC: 9287124. DOI: 10.1016/j.immuni.2022.02.005. View

11.

Li F, Lin Y, Li R, Shen X, Xiang M, Xiong G . Molecular targeted therapy for metastatic colorectal cancer: current and evolving approaches. Front Pharmacol. 2023; 14:1165666. PMC: 10622804. DOI: 10.3389/fphar.2023.1165666. View

12.

Mo S, Ma X, Li Y, Zhang L, Hou T, Han-Zhang H . Somatic POLE exonuclease domain mutations elicit enhanced intratumoral immune responses in stage II colorectal cancer. J Immunother Cancer. 2020; 8(2). PMC: 7454238. DOI: 10.1136/jitc-2020-000881. View

13.

Hornyak L, Dobos N, Koncz G, Karanyi Z, Pall D, Szabo Z . The Role of Indoleamine-2,3-Dioxygenase in Cancer Development, Diagnostics, and Therapy. Front Immunol. 2018; 9:151. PMC: 5797779. DOI: 10.3389/fimmu.2018.00151. View

14.

Muro K, Chung H, Shankaran V, Geva R, Catenacci D, Gupta S . Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016; 17(6):717-726. DOI: 10.1016/S1470-2045(16)00175-3. View

15.

Diaz Jr L, Shiu K, Kim T, Jensen B, Jensen L, Punt C . Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022; 23(5):659-670. PMC: 9533375. DOI: 10.1016/S1470-2045(22)00197-8. View

16.

Dixon K, Lahore G, Kuchroo V . Beyond T cell exhaustion: TIM-3 regulation of myeloid cells. Sci Immunol. 2024; 9(93):eadf2223. DOI: 10.1126/sciimmunol.adf2223. View

17.

Grassilli E, Cerrito M . Emerging actionable targets to treat therapy-resistant colorectal cancers. Cancer Drug Resist. 2022; 5(1):36-63. PMC: 8992594. DOI: 10.20517/cdr.2021.96. View

18.

Zhou X, Yao Z, Bai H, Duan J, Wang Z, Wang X . Treatment-related adverse events of PD-1 and PD-L1 inhibitor-based combination therapies in clinical trials: a systematic review and meta-analysis. Lancet Oncol. 2021; 22(9):1265-1274. DOI: 10.1016/S1470-2045(21)00333-8. View

19.

Taieb J, Svrcek M, Cohen R, Basile D, Tougeron D, Phelip J . Deficient mismatch repair/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment. Eur J Cancer. 2022; 175:136-157. DOI: 10.1016/j.ejca.2022.07.020. View

20.

Shaw P, Dwivedi S, Bhattacharya R, Mukherjee P, Rao G . VEGF signaling: Role in angiogenesis and beyond. Biochim Biophys Acta Rev Cancer. 2024; 1879(2):189079. DOI: 10.1016/j.bbcan.2024.189079. View