CXCR5+CD8 T cells: Potential immunotherapy targets or drivers of immune-mediated adverse events?

Christi N Turner; Genevieve N Mullins; Katrina K Hoyer

doi:10.3389/fmed.2022.1034764

CXCR5⁺CD8 T cells: Potential immunotherapy targets or drivers of immune-mediated adverse events?

Front Med (Lausanne). 2022 Oct 13:9:1034764. doi: 10.3389/fmed.2022.1034764. eCollection 2022.

Authors

Christi N Turner¹, Genevieve N Mullins¹, Katrina K Hoyer^{1

2

3}

Affiliations

¹ Quantitative and Systems Biology Graduate Program, University of California, Merced, Merced, CA, United States.
² Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA, United States.
³ Health Sciences Research Institute, University of California, Merced, Merced, CA, United States.

Abstract

CXCR5⁺CD8 T cells have attracted significant interest within multiple areas of immunology, cancer, and infection. This is in part due to their apparent dual functionality. These cells perform as cytotoxic cells in a variety of infection states including LCMV, HBV, HIV and SIV. However, CXCR5⁺CD8 T cells also associate with B cells in peripheral organs and function to stimulate B cell proliferation, antibody/B cell receptor class-switch, and antibody production. CXCR5⁺CD8 T cells are similar to CXCR5⁺CD4 T follicular helpers in their genetic make-up, B cell interactions, and functionality despite possessing elevated programmed cell death 1 and cytotoxic proteins. Within cancer CXCR5⁺CD8 T cells have risen as potential prognostic markers for overall survival and are functionally cytotoxic within tumor microenvironments. In inflammatory disease and autoimmunity, CXCR5⁺CD8 T cells are implicated in disease progression. During viral infection and cancer, CXCR5 expression on CD8 T cells generally is indicative of progenitor memory stem-like exhausted cells, which are more responsive to immune checkpoint blockade therapy. The use of immune checkpoint inhibitors to overcome immune exhaustion in cancer, and subsequent consequence of immune adverse events, highlights the dual nature of the cellular immune response. This review will detail the functionality of CXCR5⁺CD8 T cells in cancer and autoimmunity with potential repercussions during immune checkpoint blockade therapy discussed.

Keywords: CD4 T follicular helper (CD4 Tfh); CD8 Tfc; CXCR5+ CD8 T cell; T follicular helper (Tfh); autoimmune disease; immune-mediated adverse events (IMAE); immune-related adverse events (IRAE); immunotherapy (ICB).

Publication types

Review