Abstract
The clinical success of immunotherapy has revolutionized the treatment of cancer patients, bringing renewed attention to tumor-infiltrating lymphocytes (TILs) of various cancer types. Immune checkpoint blockade is effective in patients with mismatched repair defects and high microsatellite instability (dMMR-MSI-H) in metastatic colorectal cancer (CRC), leading the FDA to accelerate the approval of two programmed cell death 1 (PD-1) blocking antibodies, pembrolizumab and nivolumab, for treatment of dMMR-MSI-H cancers. In contrast, patients with proficient mismatch repair and low levels of microsatellite stability or microsatellite instability (pMMR-MSI-L/MSS) typically have low tumor-infiltrating lymphocytes and have shown unsatisfied responses to the immune checkpoint inhibitor. Different TILs environments reflect different responses to immunotherapy, highlighting the complexity of the underlying tumor-immune interaction. Profiling of TILs fundamental Indication would shed light on the mechanisms of cancer-immune evasion, thus providing opportunities for the development of novel therapeutic strategies. In this review, we summarize phenotypic diversities of TILs and their connections with prognosis in CRC and provide insights into the subsets-specific nature of TILs with different MSI status. We also discuss current clinical immunotherapy approaches based on TILs as well as promising directions for future expansion, and highlight existing clinical data supporting its use.
Highlights
Colorectal cancer (CRC) is a clinically common malignant tumor of the digestive system
Significant achievements have been witnessed in the field of colorectal cancer (CRC) immunotherapy
Monoclonal antibodies that block immune checkpoints to prevent T cell exhaustion and promote tumor destruction by cytotoxic CD8+ T cells, have been shown to be effective in mCRC patients with dMMR-microsatellite instability-high (MSI-H)
Summary
Colorectal cancer (CRC) is a clinically common malignant tumor of the digestive system. In another study evaluating the number of multiple immune cells in an in situ immune response of 490 patients with CRC, the total density of cytotoxic T cells was significantly higher in MSI samples than in MSS samples. In a large study of 125 frozen colorectal tumor specimens, immune-related genes indicated that patients with high expression of the Th17 cluster had a poor prognosis, whereas patients with high expression of the Th1 cluster had prolonged disease-free survival In addition to cytotoxic effects, NK cells have been reported to produce a large number of cytokines similar to T cells, including IL-2 [96], IL-7 [97], IL-15 [98], and IFN-g [99], to modulate adaptive immune responses and participate in other related pathways. A number of studies have elucidated the possible mechanisms of NK cells, paving the way for clinical research into NK cell-based cancer therapies, and lighting up hope for patients currently resistant to T cellbased immunotherapy
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