Longitudinal T-cell receptor repertoire analysis during neoadjuvant therapy of HER2-positive breast cancer

Purpose To analyze the peripheral blood T-cell receptor (TCR) repertoire in patients with HER2-positive breast cancer (BC), to identify markers that may aid in understanding antitumor immunity against HER2-positive BC, and to potentially predict therapy response to anti-HER2 drugs.

Materials and methods We performed next-generation high-throughput repertoire sequencing of TCR mRNA on peripheral blood samples from 11 patients with HER2-positive BC, receiving neoadjuvant anti-HER2 therapy, and 7 patients with triple-negative BC. For each patient, 10 samples were collected during neoadjuvant treatment. We compared the longitudinal TCR repertoire of the two subgroups using established and newly developed bioinformatic methods.

Results and conclusion We found a significant reduction of TCR repertoire diversity within the HER2-positive group towards the end of neoadjuvant therapy, suggesting clonal expansion in response to anti-HER2 immunotherapy. Also, we identified families of clonotypes preferentially found in patients with HER2-positive BC as compared to triple-negative BC, as well as individual clonotypes increasing or decreasing during treatment. In particular, we found that the semi-invariant TCR alpha chains of mucosal associated invariant T (MAIT) cells were present significantly more abundantly in patients with HER2-positive BC. These results suggest that the TCR repertoire may be influenced by and potentially plays a role in the response to immunotherapy for HER2-positive BC. Further research is needed to make comparisons with the TCR repertoires of healthy controls and to investigate the repertoires of tumor-infiltrating T cells.

Publikationsverlauf

Artikel online veröffentlicht:
11. Oktober 2022