CTLA4 blockade broadens the peripheral T-cell receptor repertoire.

ABSTRACT:

Purpose

To evaluate the immunomodulatory effects of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) blockade with tremelimumab in peripheral blood mononuclear cells (PBMC).

Experimental design

We used next-generation sequencing to study the complementarity-determining region 3 (CDR3) from the rearranged T-cell receptor (TCR) variable beta (V-beta) in PBMCs of 21 patients, at baseline and 30 to 60 days after receiving tremelimumab.

Results

After receiving tremelimumab, there was a median of 30% increase in unique productive sequences of TCR V-beta CDR3 in 19 out of 21 patients, and a median decrease of 30% in only 2 out of 21 patients. These changes were significant for richness (P = 0.01) and for Shannon index diversity (P = 0.04). In comparison, serially collecte

SUBMITTER: Robert L 

PROVIDER: S-EPMC4008652 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature