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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Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial. / Graeser, Monika; Feuerhake, Friedrich; Gluz, Oleg; Volk, Valery; Hauptmann, Michael; Jozwiak, Katarzyna; Christgen, Matthias; Kuemmel, Sherko; Grischke, Eva-Maria; Forstbauer, Helmut; Braun, Michael; Warm, Mathias; Hackmann, John; Uleer, Christoph; Aktas, Bahriye; Schumacher, Claudia; Kolberg-Liedtke, Cornelia; Kates, Ronald; Wuerstlein, Rachel; Nitz, Ulrike; Kreipe, Hans Heinrich; Harbeck, Nadia.
In: J IMMUNOTHER CANCER, Vol. 9, No. 5, e002198, 05.2021.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial
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
N1 - © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
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.
KW - Adult
KW - B7-H1 Antigen/metabolism
KW - Biomarkers, Tumor/metabolism
KW - CD4-Positive T-Lymphocytes/drug effects
KW - CD8-Positive T-Lymphocytes/drug effects
KW - Chemotherapy, Adjuvant
KW - Clinical Decision-Making
KW - Female
KW - Germany
KW - Humans
KW - Immunohistochemistry
KW - Lymphocytes, Tumor-Infiltrating/drug effects
KW - Middle Aged
KW - Neoadjuvant Therapy
KW - Predictive Value of Tests
KW - Programmed Cell Death 1 Receptor/metabolism
KW - Prospective Studies
KW - Time Factors
KW - Treatment Outcome
KW - Triple Negative Breast Neoplasms/drug therapy
KW - Tumor Microenvironment/immunology
U2 - 10.1136/jitc-2020-002198
DO - 10.1136/jitc-2020-002198
M3 - SCORING: Journal article
C2 - 33963012
VL - 9
JO - J IMMUNOTHER CANCER
JF - J IMMUNOTHER CANCER
SN - 2051-1426
IS - 5
M1 - e002198
ER -