Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial
In: Journal for ImmunoTherapy of Cancer, Jg. 9 (2021-05-01), Heft 5, S. e002198
Online
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Zugriff:
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.
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Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial
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Autor/in / Beteiligte Person: | Jozwiak, Katarzyna ; Forstbauer, Helmut ; Volk, Valery ; Grischke, Eva-Maria ; Schumacher, Claudia ; Uleer, Christoph ; Kreipe, Hans ; Hauptmann, Michael ; Gluz, Oleg ; Wuerstlein, Rachel ; Hackmann, John ; Braun, Michael ; Aktas, Bahriye ; Nitz, Ulrike ; Graeser, Monika ; Kates, Ronald E. ; Harbeck, Nadia ; Kuemmel, Sherko ; Kolberg-Liedtke, Cornelia ; Christgen, Matthias ; Feuerhake, Friedrich ; Warm, Mathias |
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Zeitschrift: | Journal for ImmunoTherapy of Cancer, Jg. 9 (2021-05-01), Heft 5, S. e002198 |
Veröffentlichung: | BMJ, 2021 |
Medientyp: | unknown |
ISSN: | 2051-1426 (print) |
DOI: | 10.1136/jitc-2020-002198 |
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