Cancer Research on Prevention and Treatment    2022, Vol. 49 Issue (09) : 977-981     DOI: 10.3971/j.issn.1000-8578.2022.22.0453
Research Progress on Combined Immunotherapy for Microsatellite Stable Colorectal Cancer#br#
YIN Zhucheng, LIANG Xinjun
Department of Medical Oncology, Hubei Cancer Hospital, Wuhan 430079, China
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Abstract In recent years, immunotherapy has achieved great progress in the treatment of malignant tumors and has enriched the treatment mode of many types of malignant tumors. Colorectal cancer is a common tumor worldwide. Immune checkpoint inhibitor therapy for patients with metastatic colorectal cancer (mCRC) featuring DNA mismatch repair deficiency/high microsatellite instability has significant clinical benefits, but approximately 95% of patients with mCRC are DNA mismatch repair proficient/microsatellite stable (MSS). These patients have poor response to immunotherapy. Therefore, strategies to improve the efficacy of immunotherapy in patients with this type of tumor have attracted considerable attention. This article reviews the research progress on combined immunotherapy for MSS mCRC.
Keywords Colorectal cancer      pMMR      MSS      Immunotherapy     
ZTFLH:  R735.3  
Fund:National Natural Science Foundation of China (No. 81772499, 81572287); Wuhan Science and Technology Bureau Applied Basic Research Project (No. 2020020601012250)
Issue Date: 15 September 2022
 Cite this article:   
YIN Zhucheng,LIANG Xinjun. Research Progress on Combined Immunotherapy for Microsatellite Stable Colorectal Cancer#br#[J]. Cancer Research on Prevention and Treatment, 2022, 49(09): 977-981.
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YIN Zhucheng
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[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics<br /> 2018: GLOBOCAN estimates of incidence and mortality<br /> worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,<br /> 2018, 68(6): 394-424.<br /> [2] Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients<br /> with metastatic DNA mismatch repair-deficient or microsatellite<br /> instability-high colorectal cancer (CheckMate 142): An openlabel,<br /> multicentre, phase 2 study[J]. Lancet Oncol, 2017, 18(9):<br /> 1182-1191.<br /> [3] Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with<br /> Mismatch-Repair Deficiency[J]. N Engl J Med, 2015, 372(26):<br /> 2509-2520.<br /> [4] O’Neil BH, Wallmark JM, Lorente D, et al. Safety and antitumor<br /> activity of the anti-PD-1 antibody pembrolizumab in patients<br /> with advanced colorectal carcinoma[J]. PLoS One, 2017, 12(12):<br /> e0189848.<br /> [5] Wang M, Wang S, Desai J, et al. Therapeutic strategies to remodel<br /> immunologically cold tumors[J]. Clin Transl Immunology, 2020,<br /> 9(12): e1226.<br /> [6] Chen EX, Jonker DJ, Loree J, et al. Effect of Combined Immune<br /> Checkpoint Inhibition vs. Best Supportive Care Alone in Patients<br /> with Advanced Colorectal Cancer: The Canadian Cancer Trials<br /> Group CO.26 Study[J]. JAMA Oncol, 2020, 6(6): 831-838.<br /> [7] Garralda E, Sukari A, Lakhani NJ, et al. A phase 1 first-in-human<br /> study of the anti-LAG-3 antibody MK4280 (favezelimab) plus<br /> pembrolizumab in previously treated, advanced microsatellite<br /> stable colorectal cancer[J]. J Clin Oncol, 2021, 39(15 suppl): 3584.<br /> [8] Ou DL, Chen CW, Hsu CL, et al. Regorafenib enhances antitumor<br /> immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumorassociated<br /> macrophages[J]. J Immunother Cancer, 2021, 9(3): e001657.<br /> [9] Wu RY, Kong PF, Xia LP, et al. Regorafenib Promotes Antitumor<br /> Immunity via Inhibiting PD-L1 and IDO1 Expression in<br /> Melanoma[J]. Clin Cancer Res, 2019, 25(14): 4530-4541.<br /> [10] Fukuoka S, Hara H, Takahashi N, et al. Regorafenib Plus<br /> Nivolumab in Patients With Advanced Gastric or Colorectal<br /> Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion<br /> Phase Ib Trial (REGONIVO, EPOC1603)[J]. J Clin Oncol, 2020,<br /> 38(18): 2053-2061.<br /> [11] Cousin S, Cantarel C, Guegan JP, et al. Regorafenib-Avelumab<br /> Combination in Patients with Microsatellite Stable Colorectal<br /> Cancer (REGOMUNE): A Single-arm, Open-label, PhaseⅡ<br /> Trial[J]. Clin Cancer Res, 2021, 27(8): 2139-2147.<br /> [12] Wang F, He MM, Yao YC, et al. Regorafenib plus toripalimab in<br /> patients with metastatic colorectal cancer: a phase Ib/II clinical<br /> trial and gut microbiome analysis[J]. Cell Rep Med, 2021, 2(9):<br /> 100383.<br /> [13] Kato Y, Tabata K, Kimura T, et al. Lenvatinib plus anti-PD-1<br /> antibody combination treatment activates CD8+ T cells through<br /> reduction of tumor-associated macrophage and activation of the<br /> interferon pathway[J]. PLoS One, 2019, 14(2): e0212513.<br /> [14] Gomez-Roca CA, Yanez E, Im SA, et al. LEAP-005: A phase 2<br /> multicohort study of lenvatinib plus pembrolizumab in patients<br /> with previously treated selected solid tumors-Results from the<br /> colorectal cancer cohort[J]. J Clin Oncol, 2021, 39(15suppl): 3564.<br /> [15] Wang L, Wei Y, Fang W, et al. Cetuximab Enhanced the Cytotoxic<br /> Activity of Immune Cells during Treatment of Colorectal<br /> Cancer[J]. Cell Physiol Biochem, 2017, 44(3): 1038-1050.<br /> [16] Lee MS, Loehrer PJ, Imanirad I, et al. Phase II study of<br /> ipilimumab, nivolumab, and panitumumab in patients with<br /> KRAS/NRAS/BRAF wild-type (WT) microsatellite stable (MSS)<br /> metastatic colorectal cancer (mCRC)[J]. J Clin Oncol, 2021, 39(3<br /> suppl): 7.<br /> [17] Martinelli E, Martini G, Famiglietti V, et al. Cetuximab<br /> Rechallenge Plus Avelumab in Pretreated Patients With RAS<br /> Wild-type Metastatic Colorectal Cancer: The Phase 2 Single-Arm<br /> Clinical CAVE Trial[J]. JAMA Oncol, 2021, 7(10): 1529-1535.<br /> [18] Limagne E, Euvrard R, Thibaudin M, et al. Accumulation of<br /> MDSC and Th17 Cells in Patients with Metastatic Colorectal<br /> Cancer Predicts the Efficacy of a FOLFOX-Bevacizumab Drug<br /> Treatment Regimen[J]. Cancer Res, 2016, 76(18): 5241-5252.<br /> [19] Lee WS, Yang H, Chon HJ, et al. Combination of anti-angiogenic<br /> therapy and immune checkpoint blockade normalizes vascularimmune<br /> crosstalk to potentiate cancer immunity[J]. Exp Mol<br /> Med, 2020, 52(9): 1475-1485.<br /> [20] Bourhis M, Palle J, Galy-Fauroux I, et al. Direct and Indirect<br /> Modulation of T Cells by VEGF-A Counteracted by Anti-<br /> Angiogenic Treatment[J]. Front Immunol, 2021, 12: 616837.<br /> [21] Cremolini C, Rossini D, Antoniotti C, et al. LBA20 FOLFOXIRI<br /> plus bevacizumab (bev) plus atezolizumab (atezo) versus<br /> FOLFOXIRI plus bev as first-line treatment of unresectable<br /> metastatic colorectal cancer (mCRC) patients: Results of the<br /> phase II randomized AtezoTRIBE study by GONO[J]. Ann Oncol,<br /> 2021, 32(5 suppl): S1294-S1295.<br /> [22] Fang JY, Richardson BC. The MAPK signalling pathways and<br /> colorectal cancer[J]. Lancet Oncol, 2005, 6(5): 322-327.<br /> [23] Kumar S, Principe DR, Singh SK, et al. Mitogen-Activated<br /> Protein Kinase Inhibitors and T-Cell-Dependent Immunotherapy<br /> in Cancer[J].Pharmaceuticals (Basel), 2020,13(1): 9.<br /> [24] Liao W, Overman MJ, Boutin AT, et al. KRAS-IRF2 Axis<br /> Drives Immune Suppression and Immune Therapy Resistance in<br /> Colorectal Cancer[J]. Cancer Cell, 2019, 3(4): 559-572. e7.<br /> [25] Lal N, White BS, Goussous G, et al. KRAS Mutation and<br /> Consensus Molecular Subtypes and 3 Are Independently<br /> Associated with Reduced Immune Infiltration and Reactivity in<br /> Colorectal Cancer[J]. Clin Cancer Res, 2018, 24(1): 224-233.<br /> [26] Hirano H, Takashima A, Hamaguchi T, et al. Current status and<br /> perspectives of immune checkpoint inhibitors for colorectal<br /> <p> cancer[J]. Jpn J Clin Oncol, 2020, 51(1): 10-19. </p> <p> [27] Lieu CH, Davis SL, Leong S, et al. Results from the safety leadin<br /> for a phase II study of pembrolizumab in combination with<br /> binimetinib and bevacizumab in patients with refractory metastatic<br /> colorectal cancer (mCRC)[J]. J Clin Oncol, 2020, 38(15 suppl):<br /> 4031.<br /> [28] Corcoran R, Giannakis M, Allen J, et al. SO-26 Clinical efficacy<br /> of combined BRAF, MEK, and PD-1 inhibition in BRAFV600E<br /> colorectal cancer patients[J]. Ann Oncol, 2020, 31(3 suppl):<br /> S226-S227.<br /> [29] Rodriguez-Ruiz ME, Rodriguez I, Barbes B, et al. Brachytherapy<br /> attains abscopal effects when combined with immunostimulatory<br /> monoclonal antibodies[J]. Brachytherapy, 2017, 16(6): 1246-1251.<br /> [30] Martino DM, Daviaud C, Vanpouille-Box C. Radiotherapy: An<br /> immune response modifier for immuno-oncology[J]. Semin<br /> Immunol, 2021, 52: 101474.<br /> [31]Yu J, Green MD, Li S, et al. Liver metastasis restrains<br /> immunotherapy efficacy via macrophage-mediated T cell<br /> elimination[J]. Nat Med, 2021, 27(1): 152-164.<br /> [32]Parikh AR, Clark JW, Wo JYL, et al. A phase II study of<br /> ipilimumab and nivolumab with radiation in microsatellite stable<br /> (MSS) metastatic colorectal adenocarcinoma (mCRC)[J]. J Clin<br /> Oncol, 2019, 37(15): 3514.<br /> [33] Ribas A, Dummer R, Puzanov L, et al. Oncolytic Virotherapy<br /> Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1<br /> Immunotherapy[J]. Cell, 2017, 107(6): 1109-1119.<br /> [34] Monge C, Xie C, Brar G, et al. A phase I/II study of JX-594<br /> oncolytic virus in combination with immune checkpoint inhibition<br /> in refractory colorectal cancer[J]. Eur J Cancer, 2020, 138(2<br /> suppl): S57-S58.<br /> [35] Labrijn AF, Janmaat ML, Reichert JM, et al. Bispecific antibodies:<br /> a mechanistic review of the pipeline[J]. Nat Rev Drug Discov,<br /> 2019, 18(8): 585-608.<br /> [36] Chang CH, Wang Y, Li R, et al. Combination Therapy with<br /> Bispecific Antibodies and PD-1 Blockade Enhances the Antitumor<br /> Potency of T Cells[J]. Cancer Res, 2017, 77(19): 5384-5394.<br /> [37] Ma H, Wang H, Sové RJ, et al. Combination therapy with T cell<br /> engager and PD-L1 blockade enhances the antitumor potency of T<br /> cells as predicted by a QSP model[J]. J Immunother Cancer, 2020,<br /> 8(2): e001141.<br /> [38] Bacac M, Fauti T, Sam J, et al. A Novel Carcinoembryonic<br /> Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment<br /> of Solid Tumors[J]. Clin Cancer Res, 2016, 22(13): 3286-3297.<br /> [39] Osada T, Patel SP, Hammond SA, et al. CEA/CD3-bispecific<br /> T cell-engaging (BiTE) antibody-mediated T lymphocyte<br /> cytotoxicity maximized by inhibition of both PD1 and PD-L1[J].<br /> Cancer Immunol Immunother, 2015, 64(6): 677-688.<br /> [40] Tabernero J, Melero I, Ros W, et al. Phase Ia and Ib studies of the<br /> novel carcinoembryonic Antigen (CEA) T-cell bispecific (CEA<br /> CD3 TCB) antibody as a single agent and in combination with<br /> atezolizumab: Preliminary efficacy and safety in patients with<br /> metastatic colorectal cancer (mCRC)[J]. J Clin Oncol, 2017,<br /> 35(15 suppl): 3002. </p>
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