Resistance of CD45RA- T cells to apoptosis and functional impairment, and activation of tumor-antigen specific T cells during radiation therapy of prostate cancer

Tabi, Zsuzsanna, Spary, Lisa Kate, Coleman, Sharon Louise, Clayton, Aled ORCID: https://orcid.org/0000-0002-3087-9226, Mason, Malcolm David ORCID: https://orcid.org/0000-0003-1505-2869 and Staffurth, John Nicholas ORCID: https://orcid.org/0000-0002-7834-3172 2010. Resistance of CD45RA- T cells to apoptosis and functional impairment, and activation of tumor-antigen specific T cells during radiation therapy of prostate cancer. The Journal of Immunology 185 (2) , pp. 1330-1339. 10.4049/jimmunol.1000488

Full text not available from this repository.

Abstract

The effect of radiation therapy (RT) to the pelvis on circulating T cells was studied in prostate cancer (PCa) patients to provide a baseline for a more informed design of combination radioimmunotherapy. Peripheral blood samples taken from 12 PCa patients with locally advanced tumor before, during, and after hypofractionated RT were analyzed for T cell phenotype and function. There was significantly more loss of naive and early memory compared with more differentiated T cells during RT. The proportions of annexin-V+ and Fas-expressing T cells were elevated in patients during RT and in PBMC irradiated in vitro (≤5.0 Gy), with preferential increases in CD45RA+ T cells. The baseline level of apoptosis of CD45RA− T cells increased >2-fold in the presence of an IκB-kinase inhibitor, indicating a protective effect via this pathway. T cell proliferation was impaired during RT with IL-2–dependent recovery post-RT. Recall T cell responses to common viral Ags, measured by IFN-γ production, were little affected by RT. In vitro irradiation of healthy donor PBMCs resulted in a significantly increased frequency of responding T cells, due at least partly to the preferential elimination of CD45RA+ T cells. Most importantly, antitumor CD4+ and CD8+ T cell responses were detectable after, but not before or during RT. The results indicate that generating tumor-specific T cell responses before RT and boosting their activity post-RT are ways likely to amplify the frequency and function of antitumor T cells, with implications for scheduling immunotherapy in PCa.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Last Modified:	05 Nov 2022 16:07
URI:	https://orca.cardiff.ac.uk/id/eprint/24901

Citation Data

Cited 28 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item