Immunotherapy: Recent Advances and Its Future as a Neoadjuvant, Adjuvant, and Primary Treatment in Colorectal Cancer

Abstract

Immunotherapy in colorectal cancer (CRC) has made great strides within the past decade. Immune checkpoint inhibitors are a class of immunotherapy and have been shown to greatly improve patient outcomes in mismatch repair-deficient (dMMR) CRC. Now, they are part of the standard of care for this subset of CRC. Because of this, there has been a growing interest in the efficacy and timing of immunotherapy for other subsets of CRC, including locally advanced, metastatic, and microsatellite stable (MSS). In this review, we aim to examine the three main classes of immunotherapy for CRC-immune checkpoint inhibitors (ICIs), adoptive cell transfer therapy (ACT), and tumor vaccines-and discuss the most recent advances and future directions for each.

Keywords: adoptive cell transfer therapy; colorectal cancer; immune checkpoint inhibitor; immunoexclusion; immunotherapy; tumor vaccine.

Figure 1

The principle of immunoexclusion is based on the concept that tumors can be hot, cold, or excluded based on the location and density of T cells in the tumor core and/or invasive margin of the tumor, which is defined as a 1 mm region centered on the interface of malignant cells and normal host cells. (A). Hot tumors have high T-cell density in the core of the tumor. (B). Cold tumors have low T-cell density in the core and invasive margin of the tumor. (C). Excluded tumors have high T-cell density only in the invasive margin of the tumor.