Patients burdened with rare cancers represent 55% of all gynaecological malignancies and have inferior survival outcomes compared to patients with more common cancers. A multicentre phase 2 study (CA209-538) demonstrated significant clinical efficacy in treating a range of advanced rare gynaecological malignancies with combination immunotherapy containing anti-PD-1 antibody (nivolumab) and anti-CTLA-4 antibody (ipilimumab). Although patients with hypermutated tumours are often responsive to immunotherapy, this was not seen for two patients (tumour mutation burden: 1535/MB and 1022/MB) within the trial, warranting further investigation.
Archival formalin-fixed paraffin-embedded tumour tissue from these two patients were investigated for expression of CD3, CD4, CD8, CD19, CD68, Granzyme B, FOXP3, MHC Class 1, PD-L1, and PanCK using multiplex immunohistochemistry.
The hypermutated uterine serous carcinoma was found to be heavily infiltrated by CD3+ T cells and CD4+FOXP3+ regulatory T cells, while the hypermutated ovarian carcinosarcoma demonstrated low-level T cell infiltration with an increased frequency of CD68+ macrophages. Both hypermutated tumours exhibited concomitant loss of MHC-I class expression on tumour cells, which in combination with increased numbers of regulatory T cells and/or lack of low-level T cell infiltration are likely indicators of tumour immune evasion and regulation.
Investigation of immune cell infiltration and MHC-I class expression in pre-treatment tumour tissues may aid in predicting response to combination immunotherapy.