Pushing Past the Blockade: Advancements in T Cell-Based Cancer Immunotherapies

• Published in: Frontiers in immunology 2021-11, Vol.12, p.777073-777073
• Main Authors: Waibl Polania, Jessica, Lerner, Emily C, Wilkinson, Daniel S, Hoyt-Miggelbrink, Alexandra, Fecci, Peter E
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers, Tumor; CAR (chimeric antigen receptor) T cells; Combined Modality Therapy - adverse effects; Combined Modality Therapy - methods; Disease Management; Disease Susceptibility; Humans; immune checkpoint inhibition (ICI); Immunity; Immunology; immunotherapy; Immunotherapy - adverse effects; Immunotherapy - methods; immunotherapy resistance; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Neoplasms - diagnosis; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - therapy; Prognosis; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Treatment Outcome; tumor microenvironment; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; tumor-associated macrophage (TAM); Tumor-Associated Macrophages - immunology; Tumor-Associated Macrophages - metabolism
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.777073

Successful cancer immunotherapies rely on a replete and functional immune compartment. Within the immune compartment, T cells are often the effector arm of immune-based strategies due to their potent cytotoxic capabilities. However, many tumors have evolved a variety of mechanisms to evade T cell-mediated killing. Thus, while many T cell-based immunotherapies, such as immune checkpoint inhibition (ICI) and chimeric antigen receptor (CAR) T cells, have achieved considerable success in some solid cancers and hematological malignancies, these therapies often fail in solid tumors due to tumor-imposed T cell dysfunctions. These dysfunctional mechanisms broadly include reduced T cell access into and identification of tumors, as well as an overall immunosuppressive tumor microenvironment that elicits T cell exhaustion. Therefore, novel, rational approaches are necessary to overcome the barriers to T cell function elicited by solid tumors. In this review, we will provide an overview of conventional immunotherapeutic strategies and the various barriers to T cell anti-tumor function encountered in solid tumors that lead to resistance. We will also explore a sampling of emerging strategies specifically aimed to bypass these tumor-imposed boundaries to T cell-based immunotherapies.