Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer death in the world. Immunotherapy using monoclonal antibodies, immune-checkpoint inhibitors, adoptive cell therapy, and cancer vaccines has raised great hopes for treating poor prognosis metastatic CRCs that are resistant to the conventional therapies. However, high inter-tumor and intra-tumor heterogeneity hinder the success of immunotherapy in CRC. Patients with a similar tumor phenotype respond differently to the same immunotherapy regimen. Mutation-based classification, molecular subtyping, and immunoscoring of CRCs facilitated the multi-aspect grouping of CRC patients and improved immunotherapy. Personalized immunotherapy using tumor-specific neoantigens provides the opportunity to consider each patient as an independent group deserving of individualized immunotherapy. In the recent decade, the development of sequencing and multi-omics techniques has helped us classify patients more precisely. The expansion of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. In this review article, we provided the latest findings in immunotherapy of CRC. We elaborated on the heterogeneity of CRC patients as a bottleneck of CRC immunotherapy and reviewed the latest advances in personalized immunotherapy to overcome CRC heterogeneity.

Colorectal cancer vaccines: The current scenario and future prospects

“…Carcinoembryonic antigen (CEA) and melanoma-associated antigen (MAGE) are the first TAAs ever identified and widely explored in the clinical trials of CRC vaccine (16). Other TAAs targeted for CRC treatment include mucin 1 (MUC-1), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 1 and 2 (VEGFR1, VEGFR2), transmembrane 4 superfamily member 5 protein (TM4SF5), survivin, mitotic centromere-associated kinesin (MCAK), guanylyl cyclase C (GUCY2C), and 5T4 (17)(18)(19)(20).…”

Current Targeted Therapy for Metastatic Colorectal Cancer

“…Immunotherapy is a novel treatment option against several types of tumors. Tumor immunotherapy induces an immune cell-mediated immune response through the neoantigen expressed on a broad range of tumors [84]. The success of tumor immunotherapy in achieving long-lasting antitumor responses has demonstrated that immune cells, mainly T cells, could be utilized to eliminate tumor cells [85].…”

Mechanism and strategies of immunotherapy resistance in colorectal cancer

“…With recent developments in cancer immunotherapy, both hematological and solid tumors respond to this treatment. In the last decade, immunotherapy has become popular as an alternative to surgery, chemotherapy, and radiotherapy for treating various tumors ( 3 , 4 ).…”