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Review
. 2021 May 14:22:1-12.
doi: 10.1016/j.omto.2021.05.001. eCollection 2021 Sep 24.

Advances and new frontiers for immunotherapy in colorectal cancer: Setting the stage for neoadjuvant success?

Nuttavut Sumransub  1 , Kornpong Vantanasiri  1 , Ajay Prakash  2 , Emil Lou  3
Affiliations
Review

Advances and new frontiers for immunotherapy in colorectal cancer: Setting the stage for neoadjuvant success?

Nuttavut Sumransub et al. Mol Ther Oncolytics. .

Abstract

Immunotherapy in the metastatic setting has drastically altered the landscape of treatment for various types of malignancy, including colorectal cancer. The category of immune checkpoint inhibitors has especially emerged as a class of therapy predicated on a more comprehensive understanding of immune cell-cancer cell regulation and evolution of the tumor microenvironment over time. Strategies including adoptive cellular therapies, tumor vaccines, and antibodies have also demonstrated the ability to enhance antitumor immunity. In this article, we provide a comprehensive review of the current landscape of immunotherapeutic strategies in colorectal cancer and provide insight into how these strategies may evolve in the next decade and be adapted to more localized forms of cancers of the colon and rectum. We provide particular focus on various combination approaches under investigation for reversing cancer-induced immunosuppression, especially in mismatch repair-proficient/microsatellite-stable colorectal tumors. Finally, we summarize current understanding on a recently identified integral factor in local immune regulation, the colonic microbiome. The aim of this article is to identify current challenges and barriers to improvement and to specify opportunities for applying knowledge in the immunotherapy sphere to rational design of clinical trials intended to improve survival and related outcomes in patients treated in the neoadjuvant setting.

Keywords: cellular therapy; colon cancer; colorectal cancer; immunotherapy; neoadjuvant; rectal cancer; solid tumor therapy.

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Conflict of interest statement

E.L. reports research grants from the American Association for Cancer Research (AACR-Novocure Tumor-Treating Fields Research Award); honorarium and travel expenses for a research talk at GlaxoSmithKline in 2016; honoraria and travel expenses for lab-based research talks; equipment for laboratory-based research, Novocure, LLC, 2018−present; honorarium for a panel discussion organized by Antidote Education for a continuing medical education (CME) module on diagnostics and treatment of HER2+ gastric and colorectal cancers, funded by Daiichi-Sankyo, 2021 (honorarium donated to lab); consultant, Nomocan Pharmaceuticals (unpaid); Scientific Advisory Board Member, Minnetronix, LLC, 2018−present (unpaid); consultant and speaker honorarium, Boston Scientific US, 2019; institutional principal investigator for clinical trials sponsored by Celgene, Novocure, Intima Biosciences, and the National Cancer Institute; and University of Minnesota membership in the Caris Life Sciences Precision Oncology Alliance (unpaid). The other authors declare that they have no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Metastatic pattern of CRC by histology subtypes Percentage represents colon cancer and rectal cancer, respectively. AC, adenocarcinoma; MC, mucinous carcinoma; SRCC, signet ring cell carcinoma. Data adapted from Riihimäki et al.
Figure 2
Figure 2
Adenoma-carcinoma sequence with genetic alteration pathways Chromosomal instability pathway (CIN) characterized by somatic copy number alterations with aneuploidy tumors. MSI-H is hypermutated and characterized by frameshift mutation of target genes.
Figure 3
Figure 3
Current state of immunotherapy in CRC Major modalities of immunotherapy in clinical trials include monoclonal antibodies, immune checkpoint inhibitors, cancer vaccines, adoptive cell therapies, and bispecific T cell engagers. The majority of the recent studies are investigating the efficacy of combination strategies and moving the application toward earlier-stage and neoadjuvant settings.
Figure 4
Figure 4
Anatomic distribution of CRC and their pattern of genetic mutation Genetic mutations are different in frequencies based on the location, and primary R-sided colon cancer has the highest rate of dMMR.
See this image and copyright information in PMC

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