BRAF and MEK inhibition in melanoma patients enables reprogramming of tumor infiltrating lymphocytes.

ABSTRACT:

Background

Combined inhibition of BRAF/MEK is an established therapy for melanoma. In addition to its canonical mode of action, effects of BRAF/MEK inhibitors on antitumor immune responses are emerging. Thus, we investigated the effect of these on adaptive immune responses.

Patients, methods and results

Sequential tumor biopsies obtained before and during BRAF/MEK inhibitor treatment of four (n = 4) melanoma patients were analyzed. Multiplexed immunofluorescence staining of tumor tissue revealed an increased infiltration of CD4⁺ and CD8⁺ T cells upon therapy. Determination of the T-cell receptor repertoire usage demonstrated a therapy induced increase in T-cell clonotype richness and diversity. Application of the Grouping of Lymphocyte Interactions by P

SUBMITTER: Peiffer L 

PROVIDER: S-EPMC8139931 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature