1. Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial
- Author
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Katarzyna Jozwiak, Helmut Forstbauer, Valery Volk, Eva-Maria Grischke, Claudia Schumacher, Christoph Uleer, Hans Kreipe, Michael Hauptmann, Oleg Gluz, Rachel Wuerstlein, John Hackmann, Michael Braun, Bahriye Aktas, Ulrike Nitz, Monika Graeser, Ronald E. Kates, Nadia Harbeck, Sherko Kuemmel, Cornelia Kolberg-Liedtke, Matthias Christgen, Friedrich Feuerhake, and Mathias Warm
- Subjects
CD4-Positive T-Lymphocytes ,0301 basic medicine ,Oncology ,Cancer Research ,Time Factors ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Medizin ,Triple Negative Breast Neoplasms ,CD8-Positive T-Lymphocytes ,B7-H1 Antigen ,0302 clinical medicine ,Germany ,breast neoplasms ,Tumor Microenvironment ,Immunology and Allergy ,Prospective Studies ,RC254-282 ,Triple-negative breast cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Middle Aged ,Immunohistochemistry ,Neoadjuvant Therapy ,Treatment Outcome ,medicine.anatomical_structure ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,Adjuvant ,immune evation ,Adult ,tumor ,medicine.medical_specialty ,T cell ,Clinical Decision-Making ,Immunology ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,Breast cancer ,Immune system ,Stroma ,Predictive Value of Tests ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Pharmacology ,Tumor microenvironment ,business.industry ,biomarkers ,Basic Tumor Immunology ,medicine.disease ,030104 developmental biology ,business ,CD8 - Abstract
BackgroundThe association of early changes in the immune infiltrate during neoadjuvant chemotherapy (NACT) with pathological complete response (pCR) in triple-negative breast cancer (TNBC) remains unexplored.MethodsMultiplexed immunohistochemistry was performed in matched tumor biopsies obtained at baseline and after 3 weeks of NACT from 66 patients from the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer (WSG-ADAPT-TN) trial. Association between CD4, CD8, CD73, T cells, PD1-positive CD4 and CD8 cells, and PDL1 levels in stroma and/or tumor at baseline, week 3 and 3-week change with pCR was evaluated with univariable logistic regression.ResultsCompared with no change in immune cell composition and functional markers, transition from ‘cold’ to ‘hot’ (below-median and above-median marker level at baseline, respectively) suggested higher pCR rates for PD1-positive CD4 (tumor: OR=1.55, 95% CI 0.45 to 5.42; stroma: OR=2.65, 95% CI 0.65 to 10.71) and PD1-positive CD8 infiltrates (tumor: OR=1.77, 95% CI 0.60 to 5.20; stroma: OR=1.25, 95% CI 0.41 to 3.84; tumor+stroma: OR=1.62, 95% CI 0.51 to 5.12). No pCR was observed after ‘hot-to-cold’ transition in PD1-positive CD8 cells. pCR rates appeared lower after hot-to-cold transitions in T cells (tumor: OR=0.26, 95% CI 0.03 to 2.34; stroma: OR=0.35, 95% CI 0.04 to 3.25; tumor+stroma: OR=0.00, 95% CI 0.00 to 1.04) and PD1-positive CD4 cells (tumor: OR=0.60, 95% CI 0.11 to 3.35; stroma: OR=0.22, 95% CI 0.03 to 1.92; tumor+stroma: OR=0.32, 95% CI 0.04 to 2.94). Higher pCR rates collated with ‘altered’ distribution (levels below-median and above-median in tumor and stroma, respectively) of T cell (OR=3.50, 95% CI 0.84 to 14.56) and PD1-positive CD4 cells (OR=4.50, 95% CI 1.01 to 20.14).ConclusionOur exploratory findings indicate that comprehensive analysis of early immune infiltrate dynamics complements currently investigated predictive markers for pCR and may have a potential to improve guidance for individualized de-escalation/escalation strategies in TNBC.
- Published
- 2021
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