Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part I—Colorectal Cancer: Microsatellite Instability, Testing, and Clinical Implications

Abstract

- Although the TNM classification of malignant tumor stage remains the key determinant of CRC prognosis and treatment, there are considerable stage-independent, interindividual differences in clinical outcome and therapy response by patients. In addition, MSI-H status has an important role in CRC management and can be reliably detected by molecular and immunohistochemistry techniques and genetic testing. Efforts must be made to identify whether MSI-H CRC is germline or sporadic to ensure appropriate treatment, accurate prognosis, and risk assessment for relatives. Microsatellite status has been recognized as a good prognostic indicator and is predictive of a poor response to 5-fluorouracil-based chemotherapy and a good response to programmed death ligand-1 inhibitor pembrolizumab in metastatic/refractory MSI-H CRC.

Loss of survival advantage for deficient mismatch repair in patients with advanced colorectal cancer may be caused by changes in prognostic value of CD8+T cell expression

“…Dendritic cells present TAAs to helper CD4 + T cells via the MHC-2 pathway. Helper T cells secrete interferon α, interleukins, and other substances to improve the sensitivity of tumours to toxic T cells [4]. Therefore, we also investigated the prognostic value of CD4 expression.…”

“…Tumours can express antigens, known as tumour-associated antigens (TAAs), which trigger immune responses [11,12]. Patients with dMMR present higher levels of TAAs and increased TILs than patients with proficient MMR (pMMR) [4,13]. Many studies have shown that TIL density is closely related to tumour prognosis [14,15].…”

Loss of survival advantage for deficient mismatch repair in patients with advanced colorectal cancer may be caused by changes in prognostic value of CD8+T cell

“…The Cancer Genome Atlas classi cation [2] and Consensus Molecular subtype classi cation [3] both de ne a subgroup of patients with de cient mismatch repair (dMMR) and show microsatellite instability high (MSI-H). MSI is the molecular ngerprint of dMMR [4]. Pathological features for dMMR CRC are typically associated with poor differentiation and increased tumour-in ltrating lymphocytes (TILs) [4].…”

“…MSI is the molecular ngerprint of dMMR [4]. Pathological features for dMMR CRC are typically associated with poor differentiation and increased tumour-in ltrating lymphocytes (TILs) [4]. The National Comprehensive Cancer Network guidelines [5] state that patients with stage II MSI-H have a better prognosis and do not bene t from uorouracil adjuvant therapy.…”

“…Tumours can express antigens, known as tumour-associated antigens (TAAs), which trigger immune responses [11,12]. Patients with dMMR present higher levels of TAAs and increased TILs than patients with pro cient MMR (pMMR) [4,13]. Many studies have shown that TIL density is closely related to tumour prognosis [14,15].…”