Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer
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<sup>+</sup> T cells with PD-L1<sup>+</sup> 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<sup>+</sup>HER2<sup>-</sup> 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.
Authors
- Jennifer Bolen
- Rita Nanda (ORCID: https://orcid.org/0000-0001-5248-0876)
- Angela M. DeMichele (ORCID: https://orcid.org/0000-0003-1297-4251)
- Denise M. Wolf (ORCID: https://orcid.org/0000-0002-3676-653X)
- Zelos Zhu
- Isela Gallagher
- Lajos Pusztai (ORCID: https://orcid.org/0000-0001-9632-6686)
- Lamorna Brown Swigart (ORCID: https://orcid.org/0000-0003-2076-5177)
- Emanuel F. Petricoin (ORCID: https://orcid.org/0000-0001-9146-5572)
- Scott Vandenberg (ORCID: https://orcid.org/0000-0003-0810-4544)
- Minetta C. Liu (ORCID: https://orcid.org/0000-0002-8206-5232)
- Douglas Yee (ORCID: https://orcid.org/0000-0002-3387-4009)
- Nola M. Hylton (ORCID: https://orcid.org/0000-0002-6747-1662)
- Clifford Hoyt (ORCID: https://orcid.org/0000-0001-6005-1350)
- Laura Sit (ORCID: https://orcid.org/0000-0002-4950-1434)
- Smita Asare (ORCID: https://orcid.org/0000-0001-6707-0917)
- Alexander Borowsky (ORCID: https://orcid.org/0000-0002-2510-8136)
- Christina Yau (ORCID: https://orcid.org/0000-0002-1937-0859)
- Donald A. Berry (ORCID: https://orcid.org/0000-0002-7657-3871)
- Laura Esserman
- Gillian L. Hirst (ORCID: https://orcid.org/0000-0002-4502-0035)
- Michael J. Campbell (ORCID: https://orcid.org/0000-0002-3788-9240)
- Hidetoshi Mori
- Laura van’t Veer
- Julie Wulfkuhle
- Jane Perlmutter
Institutions
- University of Minnesota (US)
- George Mason University (US)
- University of California, San Francisco (US)
- Yale University (US)
- University of Chicago (US)
- Berry & Associates (United States) (US)
- Quantum Leap Healthcare Collaborative (US)
- Mayo Clinic in Arizona (US)
- Gemini Computers (United States) (US)
- Akoya Biosciences (United States) (US)
- University of Pennsylvania (US)
- University of California, Davis (US)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2024-11-01
- DOI
- https://doi.org/10.1016/j.xcrm.2024.101799
- Citations
- 6
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 1.70
Funders
- Breast Cancer Research Foundation
- Bristol-Myers Squibb
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Celgene
- Menarini Silicon Biosystems
- Syndax Pharmaceuticals
- MacroGenics
- G1 Therapeutics
- Seagen
- Natera
- Springworks Therapeutics
- Eisai
- Symphogen
- National Institutes of Health
- Genentech
- National Cancer Institute
- Daiichi Sankyo Europe