Immune landscape and biomarkers for immuno-oncology in colorectal cancers

Abstract

Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the third leading cause of cancer-related death in Korea [1]. Because of rapid spread of colonoscopy screening, there was a general decrease in CRC until 2010. However, recent studies have reported that the decline in CRC incidence has reversed during the last few years, especially in middle-aged persons, and the occurrence of early-onset CRC has rapidly increased [2]. Most patients with CRC are diagnosed at an operable stage; however, approximately 20% of patients with stage III or high-risk stage II CRC relapse within 5 years after curative resection [3]. Moreover, the 5-year relative survival rate for metastatic CRC is 14% [2]. To improve clinical outcomes for patients with CRC, a more effective treatment modality is required to fulfill those unmet needs. Cancer is fundamentally a genetic disease since the accumulation of mutations, fusions, and copy number alterations drives tumorigenesis. However, recent research on the tumor immune microenvironment (TIME) has revealed the importance of interactions between tumor cells and surrounding immune cells in tumorigenesis [4]. Immune checkpoint inhibitor (ICI) treatment , such as anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies and anti-programmed death-1 (PD-1) antibodies, has shown marked clinical benefits in many types of cancer [5,6]. CRC also holds promise for cancer immunotherapy use, and the U.S. Food and Drug Administration (U.S. FDA) approved immunotherapeutic agents for microsatellite instability-high (MSI-H) CRC in 2017 (Fig. 1) [7,8]. In this review, we describe the landscape of the immune microenvironment in CRC and summarize the clinical usefulness of several suggested biomarkers in CRC immunotherapy. IMMUNE LANDSCAPE OF COLORECTAL CANCERS Historical use of microscopic evaluation of immune environment in CRCs To our knowledge, Spratt and Spjut [9] published the first study on integrative histologic evaluation of CRCs in 1967. In that study, the authors evaluated histologic grade, mucinous elements, depth of invasion, characteristics of tumor border, lym

Genomic and transcriptomic characterization of heterogeneous immune subgroups of microsatellite instability-high colorectal cancers

“…Similar to the generally accepted subtypes in other cancers, immune subgroups of MSI-H CRCs would be determined by multiple parameters, such as gene signatures, rather than a single discriminating factor. 6 39 This is in line with recent evidence of inconsistency and tumor-type dependency of TMB in immunotherapy responses. 40–42 …”

Tumor Mutational Burden Predicting the Efficacy of Immune Checkpoint Inhibitors in Colorectal Cancer: A Systematic Review and Meta-Analysis

“…In addition to TMB, several other biomarkers also play an important role in predicting the prognosis of colorectal cancer and the efficacy of ICI. It is reported that these biomarkers overlap in varying degrees in CRC ( 51 ). Although the expression of PD-L1 is considered to be a biomarker for predicting ICI therapy in many cancers (such as lung cancer), current studies have shown that the expression of PD-L1 has no predictive value in CRC patients treated with ICI, and the prognostic value of its overexpression varies with the status of MSI ( 2 , 28 , 52 ).…”

Association of Tumor-Infiltrating Lymphocytes With Survival in Stages II and III Colorectal Cancer

“…Certain well-documented clinical and histological risk factors are associated with a higher probability of recurrence. In stage III patients and those in stage II with risk factors, adjuvant treatment is recommended to reduce the recurrence risk [ 8 ].…”