CD20+ T cells: phenotype, origin and presence in the tumour microenvironment

Suliman, Muath Mohammed (2022). CD20+ T cells: phenotype, origin and presence in the tumour microenvironment. University of Birmingham. Ph.D.

Preview

Suliman2022PhD.pdf
Text - Accepted Version
Available under License All rights reserved.
Download (7MB) | Preview

Abstract

CD20 is well-known as a lineage marker for B cells in human, although the presence of CD20+ T cells has been reported previously (Schuh et al., 2016). In my experiments we sorted memory CD8+CD20+ and CD20- T cells and subsequently analysed TCRβ CDR3 sequences to determine clonal overlap between populations. I was able to demonstrate TCRβ CDR3 amino acid sequences within the CD20+ T cells that were not found in the CD20- T cells population, suggesting the presence of unique T cell clones. This data suggests possible thymic origin of at least some CD20+ T cells, or an early expression of CD20+ following activation of naïve T cells. This does not however refute the trogocytosis theory where some T cells acquire CD20 from B cell. I analysed a number of published mass cytometry datasets and determined that memory CD20+ T cells express higher levels of CD127, CD27, CD28, PD-1 and CD57 especially by the effector memory (Tem) and effector memory CD45RA revertant (Temra) subsets, suggesting a possible late differentiation state of the CD20+ T cells. Further phenotyping revealed a novel population of CD20+Vα7.2+CD161+ cells in the peripheral blood of healthy donors, which are potentially CD20+ mucosal-invariant T (MAIT) cells. In colon cancer, CD20+ T cells were found within tumour tissue, adjacent normal tissue and showed fewer CD20+ T cells expressing the marker CD39. This may indicate lower numbers of CD20+ T cells within tumour-reactive T cell pool and requires further investigation. Using mass cytometry datasets from colorectal cancer patients, and melanoma patients receiving anti- programmed cells death (PD-1) or anti-cytotoxic T lymphocyte-associated protein-4 (CTLA-4), CD20+ T cells showed similar phenotypes to those found in healthy peripheral blood. Importantly, they produced higher levels of cytokines compared to the CD20- T cells including; TNF-α, IFN-γ, IL-2, IL-17, and MIP-1β. My data, including both primary data and analysis of published datasets, indicates that CD20+ T cells can originate as a separate lineage, in addition to acquiring CD20 by trogocytosis. CD20+ T cells were found to be more highly differentiated, with increased cytokine production and contained a high frequency of CD20+ Vα7.2+CD161+ cells. Although there was no detectable difference in cancer, future work will be required to determine if they play any role within the tumour microenvironment or other pathological scenarios.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):