Expression data from cytotoxic T cell clone

T cells contribute to host-tumor interactions in patients with monoclonal gammopathies. Expansions of CD8+CD57+TCRV+ restricted cytotoxic T cell (CTL) clones are found in 48% of patients with multiple myeloma and confer a favorable prognosis. We now report the presence of CTL clones with varying TCRV repertoire in 70% of patients with Waldenstroms Macroglobulinaemia (WM) (n=20). Previous nucleoside analogue (NA) therapy, associated with an increased incidence of transformation to aggressive lymphoma, significantly influenced the presence of TCRV expansions (X2=11.6; P<0.001) as 83% of patients without (n=6) and only 7% with TCRV expansions (n=14) had received NA. Clonality of CD3+CD8+CD57+TCRV+ restricted CTLs were confirmed by TCRV CDR3 size analysis and direct sequencing. To characterize CTL clones, samples of CD3+CD8+CD57+TCRV+ cells were profiled using DNA microarrays and the results were validated on both gene and protein level. By gene set enrichment analysis, CTL clones not only expressed genes (GZMB, PRF1, FGFBP2) from cytotoxic pathways but also genes which suppress apoptosis, inhibit proliferation, arrest cell cycle G1/S transition and activate T cells (RAS, CSK and TOB pathways). Proliferation tracking confirmed their anergic state. Our studies demonstrate the incidence, NA sensitivity and anergic nature of clonal T cells in a B cell tumor.

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Li J, Sze DM, Brown RD, Cowley MJ, Kaplan W, Mo SL, Yang S, Aklilu E, Kabani K, Loh YS, Yamagishi T, Chen Y, Ho PJ, Joshua DE