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

Journal Article (Review;Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Waibl Polania, J; Lerner, EC; Wilkinson, DS; Hoyt-Miggelbrink, A; Fecci, PE

Published Date

  • January 2021

Published In

Volume / Issue

  • 12 /

Start / End Page

  • 777073 -

PubMed ID

  • 34868044

Pubmed Central ID

  • PMC8636733

Electronic International Standard Serial Number (EISSN)

  • 1664-3224

International Standard Serial Number (ISSN)

  • 1664-3224

Digital Object Identifier (DOI)

  • 10.3389/fimmu.2021.777073

Language

  • eng