Abstract
Over the last few decades, major efforts in cancer research and treatment have intensified. Apart from standard chemotherapy approaches, immunotherapy has gained substantial traction. Personalized immunotherapy has become an important tool for cancer therapy with the discovery of immune checkpoint inhibitors. Traditionally, tumor-associated antigens are used in immunotherapy-based treatments. Nevertheless, these antigens lack specificity and may have increased toxicity. With the advent of next-generation technologies, the identification of new tumor-specific antigens is becoming more important. In colorectal cancer, several tumor-specific antigens were identified and functionally validated. Multiple clinical trials from vaccine-based and adoptive cell therapy utilizing tumor-specific antigens have commenced. Herein, we will summarize the current landscape of tumor-specific antigens particularly in colorectal cancer.
Highlights
Colorectal cancer (CRC) is a collective term that represents both colon and rectal cancers
This study showed that microsatellite instability (MSI)-CRCs have different immune microenvironments comprising of tumor neoantigen-specific CD8 T cells, which could be used to further advance immunotherapy in this specific subset of tumors, including in Lynch syndrome [73]
Germany performed frameshift-derived peptides (FSP)-based studies on several genes including TGFBRII in MSI-CRC [77]. This particular study focused on three different peptides deriving from TGFBRII mutants and they successfully showed that T cells induced FSP02 peptide were able to lyse cell lines harboring the mutant in an human leukocyte antigen (HLA)-A201 dependent manner [77]
Summary
Colorectal cancer (CRC) is a collective term that represents both colon and rectal cancers. Vaccines 2020, 8, 371 priming, mediated by antigen-presenting cells (APCs) such as dendritic cells (DCs) [7]. The activated CD8+ T cells or CTLs can perform cytotoxic activity against the specific antigen-bearing tumor cells [8]. Infiltrating CTLs uses two pathways to mediate tumor cytolysis, which is Fas ligand (FasL)—mediated apoptosis and granule exocytosis pathways [10]. The binding of FasL of CTL to the Fas protein on tumor cells initiates a caspase cascade that eventually leads to cellular apoptosis [11]. It has been demonstrated that one of the roles of PFN is to induce tumor apoptosis [14] These released granzymes enter the tumor cells and induce multiple processes such as cytolysis, extracellular matrix degeneration, inflammation and extravasation [15]. The understanding of the role of cytotoxic T cells in tumor regression allows researchers to investigate and improve the efficacy of T cells in treating cancer
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