探究帕博利珠单抗对新诊断苗勒管癌肿瘤免疫特征影响的初步研究

This pilot window of opportunity study was conducted to assess feasibility, toxicity, and changes in immune parameters in response to one dose of the PD-1 inhibitor, pembrolizumab, in patients newly diagnosed with mullerian epithelial cancers.

Eligible patients received pembrolizumab 200 mg IV once 7 days prior to further standard therapy, including adjuvant chemotherapy. Tissue and blood were collected before and 7 days after pembrolizumab administration. Primary endpoints included change in tumor infiltrating lymphocytes (TIL), feasibility, and toxicity based on frequency and severity of adverse events. Exploratory objectives included tumor assessment of immunohistochemical PD-L1 staining using a quantitative modified proportion score and qualitative assessment of immune presence at the stromal interface. Measurement of cytokine levels and digital spatial profiling were performed from plasma and tissue samples, respectively, before and after pembrolizumab.

Fifteen patients enrolled and received pembrolizumab. TIL levels changed in 4 of 11 paired sets, with 3 decreasing and 1 increasing post-treatment. PD-L1 modified proportion score increased in 7 cases, decreased in 2, and remained unchanged in 2. The stromal interface switched from negative to positive in 3 cases. Collectively, 8 of 10 assessable tumor pairs demonstrated either an increase in PD-L1 modified proportion score or the stromal interface switched from negative to positive. Circulating CXCL10 and TNF levels increased after pembrolizumab in patients with response, but decreased in the one patient with progression on adjuvant chemotherapy. Digital spatial profiling showed increased IDO1 protein expression in immune and tumor compartments after treatment.

A single dose of pembrolizumab increased PD-L1 modified proportion score and/or stromal interface immune cells suggesting potential for local tumor immunologic recruitment. Additionally, increases in systemic inflammation, measured by cytokine production and differential IDO1 expression, reflect an interferon response. These hypothesis-generating data need to be confirmed and validated in larger subsets.