Immune Biomarkers as Predictors of Response to Checkpoint Blockade in Breast Cancer

The following article features coverage from the American Association for Cancer Research (AACR) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Results of this study showed several biomarkers of the immune microenvironment in pretreatment breast cancer tumor specimens were positively or negatively associated with achievement of a pathologic complete response (pCR) in patients subsequently receiving neoadjuvant treatment with the programmed cell death 1 inhibitor (PD-1), pembrolizumab. The findings of this study were presented at the American Association for Cancer Research (AACR) Annual Meeting 2019. 

The identification of robust predictors of response to immune checkpoint blockade is an ongoing area of research. In this context, multiplex multispectral imaging was performed to evaluate potential biomarkers of immune response in immunostained formalin-fixed paraffin embedded (FFPE) breast cancer tumor specimens obtained from women with nonmetastatic breast cancer enrolled in a pembrolizumab arm of the phase 2, randomized “Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY2)” trial (ClinicalTrials.gov Identifier: NCT01042379). 

Biomarkers assessed included CD3, CD8, FoxP3, CD68, PD-1, PD-L1, and cytokeratins; cell counts and densities of a variety of different immune cell types were also determined. In addition, assessments of the spatial proximities of different immune cell types from cancer cells were performed. 

Key findings from this study were that the density of T cells, Treg cell density, and the density of PD-1–positive T cells — as well as the spatial distribution of CD3-positive T cells in proximity to cancer cells — were positively correlated with pCR. In contrast, the ratio of macrophages to Tc cells was negatively correlated with pCR.   

“These results demonstrate the utility of characterizing the immune microenvironment, in the context of therapy with immuno-oncology agents, not only to predict response, but to gain insight and learn [h]ow to potentiate agents and combinations,” the authors concluded.

Read more of Cancer Therapy Advisor‘s coverage of AACR 2019 meeting by visiting the conference page.

Reference

1. Campbell MJ, Yau C, Bolen J et al. Analysis of immune cell infiltrates as predictors of response to the checkpoint inhibitor pembrolizumab in the neoadjuvant I-SPY2 trial. Presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Abstract CT003.