Abstract IA31: What limits the response of breast cancer to immunotherapy?

Checkpoint blockade has been evaluated successfully in the classically immunogenic solid tumor types such as melanoma and renal cell carcinoma, as well as in hematologic malignancies. While a large degree of T-cell infiltrate has been observed in primary breast cancers, particularly triple-negative and Her2-positive subtypes, efficacy with checkpoint blockade as monotherapy has been modest so far in studies in advanced disease. Given that higher levels of T-cell infiltrate have been associated with improved prognoses and response to cytotoxic chemotherapy, my lab has hypothesized that these T cells would have functional characteristics that would be important in immunosurveillance of breast cancer. We have characterized these T cells using methods such as multiplex immunohistochemistry, bulk gene expression, and flow cytometry, as well as single-cell transcriptomic sequencing in order to better characterize these T cells. We have also observed lower levels of immune infiltrate in samples from metastatic breast cancer lesions, suggesting that the primary disease setting may be the most amenable to checkpoint inhibitor approaches. Data currently support that line of therapy in the advanced breast cancer setting; tumor burden and T-cell infiltrate predict for higher response rates to PD-1 blockade as monotherapy. Finally, given that most patients with advanced breast cancer have a “noninflamed” tumor microenvironment, my lab has been evaluating how therapeutics can modulate the immune microenvironment. Certain agents such as MEK inhibitors as well as combination targeted therapies can potentially increase tumor immunogenicity as well as synergize well with immunotherapies. These combinatorial approaches may serve to increase the response rate of immunotherapy in breast cancer patients as well as prolong duration of response in patients treated with new therapeutic agents. Citation Format: Sherene Loi. What limits the response of breast cancer to immunotherapy? [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA31.