Journal of Shanghai Jiao Tong University (Medical Science) >

2023 , Vol. 43 >Issue 2: 250 - 255

DOI: https://doi.org/10.3969/j.issn.1674-8115.2023.02.016

Review

Research progress of immune checkpoint inhibitors in the treatment of metastatic colorectal cancer

  • Juanjuan TU ,
  • Zhiming JIN
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  • Department of General Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
JIN Zhiming, E-mail: jzmgyp@hotmail.com.

Received date: 2022-05-20

  Accepted date: 2022-10-27

  Online published: 2023-02-28

Supported by

Shanghai Municipality Science and Technology Commission(16140900302)

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Abstract

Colorectal cancer (CRC) is a common malignancy with a high incidence of metastatic events in China and the world. Immunotherapy has received increasing attention as an emerging therapy in the treatment of metastatic colorectal cancer (mCRC). Immune checkpoint inhibitor (ICI) is one of the important methods, mainly represented by programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies. The strong potential of ICIs in the treatment of mCRC has been confirmed by completed and ongoing clinical trials. The U.S. Food and Drug Administration has approved some ICIs for the first-line treatment of microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) mCRC. ICI cannot yet replace the conventional therapy in the treatment of microsatellite stable (MSS)/mismatch repair proficient (pMMR) mCRC, but an increasing number of ICI combination programs have entered the clinical trial phase and have initially shown good clinical efficacy and application prospects. Finding new markers to identify potentially beneficial patients, validating new combination regimens, and developing new immune checkpoints are all important to the future of ICI research.

Key words： metastatic colorectal cancer; immune checkpoint inhibitor; programmed death-1 (PD-1)

Cite this article

Juanjuan TU , Zhiming JIN . Research progress of immune checkpoint inhibitors in the treatment of metastatic colorectal cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023 , 43(2) : 250 -255 . DOI: 10.3969/j.issn.1674-8115.2023.02.016

References

1 中华人民共和国国家卫生健康委员会. 中国结直肠癌诊疗规范(2020年版)[J]. 中华外科杂志, 2020, 58(8): 561-585.
1 National Health Commission of the People's Republic of China. Chinese protocol of diagnosis and treatment of colorectal cancer (2020 edition)[J]. Chinese Journal of Surgery, 2020, 58(8): 561-585.
2 VAN CUTSEM E, CERVANTES A, ADAM R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer[J]. Ann Oncol, 2016, 27(8): 1386-1422.
3 ZHANG Y Y, SUN Z, MAO X X, et al. Impact of mismatch-repair deficiency on the colorectal cancer immune microenvironment[J]. Oncotarget, 2017, 8(49): 85526-85536.
4 MABY P, TOUGERON D, HAMIEH M, et al. Correlation between density of CD8+ T-cell infiltrate in microsatellite unstable colorectal cancers and frameshift mutations: a rationale for personalized immunotherapy[J]. Cancer Res, 2015, 75(17): 3446-3455.
5 MARCUS L, LEMERY S J, KEEGAN P, et al. FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors[J]. Clin Cancer Res, 2019, 25(13): 3753-3758.
6 BENSON A B, VENOOK A P, AL-HAWARY M M, et al. Colon cancer, version 2.2021, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2021, 19(3): 329-359.
7 KIM J H, KIM S Y, BAEK J Y, et al. A phase Ⅱ study of avelumab monotherapy in patients with mismatch repair-deficient/microsatellite instability-high or POLE-mutated metastatic or unresectable colorectal cancer[J]. Cancer Res Treat, 2020, 52(4): 1135-1144.
8 ANDRé T, SHIU K K, KIM T W, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer[J]. N Engl J Med, 2020, 383(23): 2207-2218.
9 GOMAR M, NAJAFI M, AGHILI M, et al. Durable complete response to pembrolizumab in microsatellite stable colorectal cancer[J]. Daru, 2021, 29(2): 501-506.
10 HAAG G M, SPRINGFELD C, GRüN B, et al. Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer: the PICCASSO phase Ⅰ trial[J]. Eur J Cancer, 2022, 167: 112-122.
11 OVERMAN M J, MCDERMOTT R, LEACH J L, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study[J]. Lancet Oncol, 2017, 18(9): 1182-1191.
12 KIM R D, KOVARI B P, MARTINEZ M, et al. A phase Ⅰ/Ⅰb study of regorafenib and nivolumab in mismatch repair proficient advanced refractory colorectal cancer[J]. Eur J Cancer, 2022, 169: 93-102.
13 DESAI J, DEVA S, LEE J S, et al. Phase ⅠA/ⅠB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors[J]. J Immunother Cancer, 2020, 8(1): e000453.
14 TAPIA RICO G, PRICE T J. Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential[J]. Expert Opin Biol Ther, 2018, 18(4): 449-457.
15 ENG C, KIM T W, BENDELL J, et al. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial[J]. Lancet Oncol, 2019, 20(6): 849-861.
16 METTU N B, OU F S, ZEMLA T J, et al. Assessment of capecitabine and bevacizumab with or without atezolizumab for the treatment of refractory metastatic colorectal cancer: a randomized clinical trial[J]. JAMA Netw Open, 2022, 5(2): e2149040.
17 TA?EB J, ANDRé T, EL HAJBI F, et al. Avelumab versus standard second line treatment chemotherapy in metastatic colorectal cancer patients with microsatellite instability: the SAMCO-PRODIGE 54 randomised phase Ⅱ trial[J]. Dig Liver Dis, 2021, 53(3): 318-323.
18 MARTINELLI E, MARTINI G, FAMIGLIETTI V, et al. Cetuximab rechallenge plus avelumab in pretreated patients with RAS wild-type metastatic colorectal cancer: the phase 2 single-arm clinical CAVE trial[J]. JAMA Oncol, 2021, 7(10): 1529-1535.
19 VAN DEN EYNDE M, HUYGHE N, DE CUYPER A, et al. Interim analysis of the AVETUXIRI trial: avelumab combined with cetuximab and irinotecan for treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC)—a proof of concept, open-label, nonrandomized phase Ⅱa study[J]. J Clin Oncol, 2021, 39(3_suppl): 80.
20 MORSE M A, HOCHSTER H, BENSON A. Perspectives on treatment of metastatic colorectal cancer with immune checkpoint inhibitor therapy[J]. Oncologist, 2020, 25(1): 33-45.
21 SUZUKI S, KAWAKAMI H, MIIKE T, et al. Complete remission of colon cancer with ipilimumab monotherapy[J]. Intern Med, 2021, 60(6): 957-958.
22 LENZ H J, VAN CUTSEM E, LUISA LIMON M, et al. First-line nivolumab plus low-dose ipilimumab for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the phase Ⅱ CheckMate 142 study[J]. J Clin Oncol, 2022, 40(2): 161-170.
23 FUMET J D, ISAMBERT N, HERVIEU A, et al. Phase Ⅰb/Ⅱ trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4) combined with FOLFOX in patients with metastatic colorectal cancer[J]. ESMO Open, 2018, 3(4): e000375.
24 CHEN E X, JONKER D J, LOREE J M, et al. Effect of combined immune checkpoint inhibition vs best supportive care alone in patients with advanced colorectal cancer: the Canadian cancer trials group CO.26 study[J]. JAMA Oncol, 2020, 6(6): 831-838.
25 SEGAL N H, CERCEK A, KU G, et al. Phase Ⅱ single-arm study of durvalumab and tremelimumab with concurrent radiotherapy in patients with mismatch repair-proficient metastatic colorectal cancer[J]. Clin Cancer Res, 2021, 27(8): 2200-2208.
26 LIANG R P, ZHU X D, LAN T Y, et al. TIGIT promotes CD8+T cells exhaustion and predicts poor prognosis of colorectal cancer[J]. Cancer Immunol Immunother, 2021, 70(10): 2781-2793.
27 THIBAUDIN M, LIMAGNE E, HAMPE L, et al. Targeting PD-L1 and TIGIT could restore intratumoral CD8 T cell function in human colorectal cancer[J]. Cancer Immunol Immunother, 2022, 71(10): 2549-2563.
28 KOYAMA S, AKBAY E A, LI Y Y, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints[J]. Nat Commun, 2016, 7: 10501.
29 MA Q, LIU J N, WU G L, et al. Co-expression of LAG3 and TIM3 identifies a potent Treg population that suppresses macrophage functions in colorectal cancer patients[J]. Clin Exp Pharmacol Physiol, 2018, 45(10): 1002-1009.
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