Sistema de Salut de Catalunya
Institut Català de la Salut
[Dent R] Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore. [Cortés J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. International Breast Cancer Center, Quironsalud Group, Barcelona, Spain. Department of Medicine, Faculty of Biomedical and Health Sciences, European University of Madrid, Madrid, Spain. [Park YH] Department of Medicine, Division of Hematology Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. [Muñoz Couselo E] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Kim SB] Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. [Sohn J] Department of Internal Medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
Vall d'Hebron Barcelona Hospital Campus
2025-04-14T09:40:38Z
2025-04-14T09:40:38Z
2025-03-11
Immunohistochemistry; Triple-negative breast cancer; Tumor microenvironment
Immunohistoquímica; Càncer de mama triple negatiu; Microambient tumoral
Inmunohistoquímica; Cáncer de mama triple negativo; Microambiente tumoral
Background The multicohort, open-label, phase 1b KEYNOTE-173 study was conducted to investigate pembrolizumab plus chemotherapy as neoadjuvant therapy for triple-negative breast cancer (TNBC). This exploratory analysis evaluated features of the tumor microenvironment that might be predictive of response. Methods Cell fractions from 20 paired samples collected at baseline and after one cycle of neoadjuvant pembrolizumab prior to chemotherapy initiation were analyzed by spatial localization (tumor compartment, stromal compartment, or sum of tumor and stromal compartments [total tumor]) using three six-plex immunohistochemistry panels with T-cell, myeloid cell, and natural killer cell components. Area under the receiver operating characteristic curve (AUROC) was used to assess associations between immune subsets and gene expression signatures (T-cell–inflamed gene expression profile [TcellinfGEP] and 10 non-TcellinfGEP signatures using RNA sequencing) and pathologic complete response (pCR). Results At baseline, six immune subsets quantitated within the tumor compartment showed AUROC with 95% CIs not crossing 0.5, including CD11c+ cells (macrophage and dendritic cell [DC]: AUROC, 0.85; 95% confidence interval [CI] 0.63–1.00), CD11c+/MHCII+/CD163−/CD68− cells (DC: 0.76; 95% CI, 0.53–0.99), CD11c+/MHCII−/CD163−/CD68− cells (nonactivated/immature DC: 0.80; 95% CI 0.54–1.00), and CD11c+/CD163+ cells (M2 macrophage: 0.77; 95% CI 0.55–0.99). Other associations with pCR included baseline CD11c+/MHCII−/CD163−/CD68− (nonactivated/immature DC) within the total tumor (AUROC, 0.76; 95% CI 0.51–1.00) and the baseline CD11c/CD3 ratio within the tumor compartment (0.75; 95% CI 0.52–0.98). Changes in immune subsets following one cycle of pembrolizumab were not strongly associated with pCR. Although T-cell associations were relatively weak, specific CD8 subsets trended toward association. The AUROC for discriminating pCR based on TcellinfGEP was 0.55 (95% CI 0.25–0.85); when detrended by TcellinfGEP, AUROC varied for the non-TcellinfGEP signatures. TcellinfGEP expression trended higher in responders than in nonresponders when evaluating pCR. Conclusions Myeloid cell populations within the tumor compartment at baseline and TcellinfGEP show a promising trend toward an association with pCR in a small subgroup of patients with early-stage TNBC treated with neoadjuvant pembrolizumab plus chemotherapy. Trial registration ClinicalTrials.gov, NCT02622074; registration date, December 2, 2015.
Funding for this research was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Article
Published version
English
Mama - Càncer - Tractament; Quimioteràpia combinada; Anticossos monoclonals - Ús terapèutic; Mama - Càncer - Aspectes genètics; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized; Other subheadings::Other subheadings::/therapeutic use; DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada; FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::tratamiento neoadyuvante; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados; Otros calificadores::Otros calificadores::/uso terapéutico; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
BMC
Breast Cancer Research;27
https://doi.org/10.1186/s13058-024-01946-y
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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