Campbell et al. analyzed biomarkers in pretreatment biopsies from patients with breast cancer in the I-SPY 2 trial (TN and HR+HER2- subtypes) to investigate immunological correlates of response to neoadjuvant anti-PD-1 therapy in the TME. Using 3 multiplex platforms, 126 biomarkers were evaluated and 56 were significantly associated with response to pembrolizumab. Tumors with high TILs and close spatial proximity of PD-1+ T cells and PD-L1+ cells (immune and tumor cells) correlated with a good response to pembrolizumab, including the TN and HR+HER2- subtypes, although different patterns of response were seen with different receptor subtypes.
Contributed by Katherine Turner
ABSTRACT: Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR). Interestingly, these differ by breast cancer receptor subtype. Measures of the spatial distributions of immune cells within the tumor microenvironment, in particular colocalization or close spatial proximity of PD-1+ T cells with PD-L1+ cells (immune and tumor cells), are significantly associated with response in the overall cohort as well as the in the triple negative (TN) and HR+HER2− subtypes. Our findings indicate that biomarkers associated with immune cell signaling, immune cell densities, and spatial metrics are predictive of neoadjuvant ICB efficacy in breast cancer.
Author Info: (1) Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA (2) Department of Laboratory Medicine, University of California, San Francisco, San
Author Info: (1) Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA (2) Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA (3) Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA (4) Biospecimen Resource Program (BIOS), University of California, San Francisco, San Francisco, CA 94143, USA (5) Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA (6) Akoya Biosciences, Marlborough, MA 01752, USA (7) Center for Immunology and Infectious Diseases, University of California, Davis, Davis, CA 95616, USA (8) Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA 95817, USA (9) Gemini Group, Ann Arbor, MI 48107, USA (10) Quantum Leap Healthcare Collaborative, San Francisco, CA 94118, USA (11) Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA (12) Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA (13)
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA (14) Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA (15) Department of Radiology, University of California, San Francisco, San Francisco, CA 94143, USA (16) Yale School of Medicine, Yale University, New Haven, CT 06510, USA (17) Berry Consultants, LLC, Austin, TX 78746, USA
