Seminoma patients as untapped reservoir of cancer-testis antigen specific T cells for immunotherapy

Ikrom, Ika Nurlaila BT Mochammad (2020). Seminoma patients as untapped reservoir of cancer-testis antigen specific T cells for immunotherapy. University of Birmingham. Ph.D.

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Abstract

Testicular cancer is a common tumour of younger men and although chemotherapy is effective, tumour-specific immune responses may be important. Previous work from our group demonstrated that patients have activated T cells in blood and functional responses to MAGE proteins.

I analysed the phenotype, checkpoint expression and function of T cells within blood from patients with seminoma or non-seminomatous tumours. No differences in T cell subsets were seen compared to healthy donors but CD27- B cells were increased and CD16 was reduced on CD56Dim NK cells. A distinctive pattern of immune checkpoint expression was observed with increased expression of Tim-3, LAG-3 and CTLA-4. This suggests some degree of T cell exhaustion although functional analysis showed broad cytokine responses after mitogenic stimulation. However, small numbers of T cells that were spontaneously producing IL-17, IL-21 or IL-10 were found, indicating baseline T cell stimulation.

In order to investigate novel approaches to identify and isolate MAGE-specific T cells I utilized cytokine secretion. This showed that TNF-α production was the most sensitive assay and, combined with CD107a, identified strong MAGE responses in two donors. Using a matrix of peptide pools I was able to isolate and define a potential novel epitope from MAGE-A4.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):