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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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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, Jahrgang 9, Nr. 5, e002198, 05.2021.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Graeser, M, Feuerhake, F, Gluz, O, Volk, V, Hauptmann, M, Jozwiak, K, Christgen, M, Kuemmel, S, Grischke, E-M, Forstbauer, H, Braun, M, Warm, M, Hackmann, J, Uleer, C, Aktas, B, Schumacher, C, Kolberg-Liedtke, C, Kates, R, Wuerstlein, R, Nitz, U, Kreipe, HH & Harbeck, N 2021, 'Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial', J IMMUNOTHER CANCER, Jg. 9, Nr. 5, e002198. https://doi.org/10.1136/jitc-2020-002198

APA

Graeser, M., Feuerhake, F., Gluz, O., Volk, V., Hauptmann, M., Jozwiak, K., Christgen, M., Kuemmel, S., Grischke, E-M., Forstbauer, H., Braun, M., Warm, M., Hackmann, J., Uleer, C., Aktas, B., Schumacher, C., Kolberg-Liedtke, C., Kates, R., Wuerstlein, R., ... Harbeck, N. (2021). Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial. J IMMUNOTHER CANCER, 9(5), [e002198]. https://doi.org/10.1136/jitc-2020-002198

Vancouver

Graeser M, Feuerhake F, Gluz O, Volk V, Hauptmann M, Jozwiak K et al. Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial. J IMMUNOTHER CANCER. 2021 Mai;9(5). e002198. https://doi.org/10.1136/jitc-2020-002198

Bibtex

@article{5ee6f29bdba74452be3280a2abf542c4,
title = "Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial",
abstract = "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.",
keywords = "Adult, B7-H1 Antigen/metabolism, Biomarkers, Tumor/metabolism, CD4-Positive T-Lymphocytes/drug effects, CD8-Positive T-Lymphocytes/drug effects, Chemotherapy, Adjuvant, Clinical Decision-Making, Female, Germany, Humans, Immunohistochemistry, Lymphocytes, Tumor-Infiltrating/drug effects, Middle Aged, Neoadjuvant Therapy, Predictive Value of Tests, Programmed Cell Death 1 Receptor/metabolism, Prospective Studies, Time Factors, Treatment Outcome, Triple Negative Breast Neoplasms/drug therapy, Tumor Microenvironment/immunology",
author = "Monika Graeser and Friedrich Feuerhake and Oleg Gluz and Valery Volk and Michael Hauptmann and Katarzyna Jozwiak and Matthias Christgen and Sherko Kuemmel and Eva-Maria Grischke and Helmut Forstbauer and Michael Braun and Mathias Warm and John Hackmann and Christoph Uleer and Bahriye Aktas and Claudia Schumacher and Cornelia Kolberg-Liedtke and Ronald Kates and Rachel Wuerstlein and Ulrike Nitz and Kreipe, {Hans Heinrich} and Nadia Harbeck",
note = "{\textcopyright} 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.",
year = "2021",
month = may,
doi = "10.1136/jitc-2020-002198",
language = "English",
volume = "9",
journal = "J IMMUNOTHER CANCER",
issn = "2051-1426",
publisher = "BioMed Central Ltd.",
number = "5",

}

RIS

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 -