PT  - JOURNAL ARTICLE
AU  - Graeser, Monika
AU  - Feuerhake, Friedrich
AU  - Gluz, Oleg
AU  - Volk, Valery
AU  - Hauptmann, Michael
AU  - Jozwiak, Katarzyna
AU  - Christgen, Matthias
AU  - Kuemmel, Sherko
AU  - Grischke, Eva-Maria
AU  - Forstbauer, Helmut
AU  - Braun, Michael
AU  - Warm, Mathias
AU  - Hackmann, John
AU  - Uleer, Christoph
AU  - Aktas, Bahriye
AU  - Schumacher, Claudia
AU  - Kolberg-Liedtke, Cornelia
AU  - Kates, Ronald
AU  - Wuerstlein, Rachel
AU  - Nitz, Ulrike
AU  - Kreipe, Hans Heinrich
AU  - Harbeck, Nadia
TI  - Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial
AID  - 10.1136/jitc-2020-002198
DP  - 2021 May 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e002198
VI  - 9
IP  - 5
4099  - http://jitc.bmj.com/content/9/5/e002198.short
4100  - http://jitc.bmj.com/content/9/5/e002198.full
SO  - J Immunother Cancer2021 May 01; 9
AB  - Background The 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.Methods Multiplexed 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.Results Compared 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).Conclusion Our 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.Data used for this analysis are available upon reasonable request to the corresponding author.