Dynamics of genomic and immune responses during primary immunotherapy resistance in mismatch repair-deficient tumors.

ABSTRACT: Mismatch repair-deficient (dMMR) cancers generate a substantial number of immunogenic neoantigens, rendering them sensitive to immunotherapy. Yet, there is considerable variability in responses, and roughly one-half of dMMR cancers are refractory to immunotherapy. Here we study a patient with dMMR lung cancer refractory to immunotherapy. The tumor exhibited typical dMMR molecular features, including exceptionally high frameshift insertions and deletions (indels). Despite the treatment inducing abundant intratumoral T-cell infiltrates, it failed to elicit tumor regression, pointing to the T cells lacking cytotoxic activity. A post-treatment tumor demonstrated compound heterozygous frameshift deletions located upstream of the kinase domain in the gene encoding JAK1 protein, down-regulation o

SUBMITTER: Takahashi N 

PROVIDER: S-EPMC7552928 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature