A phase Ib/II trial of atezolizumab with cobimetinib or idasanutlin in metastatic estrogen receptor positive breast cancer.

Despite the availability of numerous treatment options for metastatic estrogen receptor positive breast cancer, additional strategies are needed, particularly when tumors become endocrine resistant. This phase Ib/II study examined the clinical activity and safety of the novel combination of atezolizumab with molecularly targeted therapy inhibiting 1) the Ras/Raf/MEK signaling pathway with cobimetinib in TP53-mutant tumors (arm COBI) or 2) the TP53 regulator MDM2 with idasanutlin in TP53-wild-type tumors (arm IDA). Twelve patients were enrolled before the study closed early due to slow accrual.

In Situ Detection of Individual Classic MHC-I Gene Products in Cancer.

Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated antigens or neoantigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin fixation, complicates detection by IHC.