Distinct profiles of proliferating CD8+/TCF1+ T cells and CD163+/PD-L1+ macrophages predict risk of relapse differently among treatment-naïve breast cancer subtypes.

Autor: Ntostoglou K; Department of Histopathology, Biomedicine Group of Health Company, 15626, Athens, Greece.; Medical School, National and Kapodistrian University of Athens, 11527, Goudi, Athens, Greece., Theodorou SDP; Medical School, National and Kapodistrian University of Athens, 11527, Goudi, Athens, Greece., Proctor T; Institute of Medical Biometry, University of Heidelberg, 69120, Heidelberg, Germany., Nikas IP; Medical School, University of Cyprus, 2029, Nicosia, Cyprus., Awounvo S; Institute of Medical Biometry, University of Heidelberg, 69120, Heidelberg, Germany., Sepsa A; Department of Anatomic Pathology, Metropolitan Hospital, 9 Ethnarchou Makariou & 1 E. Venizelou Street, Neo Faliro, 18547, Piraeus, Greece., Georgoulias V; Hellenic Research Oncology Group, 11474, Athens, Greece., Ryu HS; Department of Pathology, College of Medicine, Seoul National University Hospital, 03080, Seoul, Republic of Korea., Pateras IS; 2nd Department of Pathology, Medical School, 'Attikon' University Hospital, National and Kapodistrian University of Athens, 124 62, Athens, Greece. ipateras@med.uoa.gr., Kittas C; Department of Histopathology, Biomedicine Group of Health Company, 15626, Athens, Greece.; Medical School, National and Kapodistrian University of Athens, 11527, Goudi, Athens, Greece.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2024 Feb 13; Vol. 73 (3), pp. 46. Date of Electronic Publication: 2024 Feb 13.
DOI: 10.1007/s00262-024-03630-8
Abstrakt: Immunophenotypic analysis of breast cancer microenvironment is gaining attraction as a clinical tool improving breast cancer patient stratification. The aim of this study is to evaluate proliferating CD8 + including CD8 + TCF1 + Τ cells along with PD-L1 expressing tissue-associated macrophages among different breast cancer subtypes. A well-characterized cohort of 791 treatment-naïve breast cancer patients was included. The analysis demonstrated a distinct expression pattern among breast cancer subtypes characterized by increased CD8 + , CD163 + and CD163 + PD-L1 + cells along with high PD-L1 status and decreased fraction of CD8 + Ki67 + T cells in triple negative (TNBC) and HER2 + compared to luminal tumors. Kaplan-Meier and Cox univariate survival analysis revealed that breast cancer patients with high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + cells, PD-L1 score and CD163 + PD-L1 + cells are likely to have a prolonged relapse free survival, while patients with high CD163 + cells have a worse prognosis. A differential impact of high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + T cells, CD163 + PD-L1 + macrophages and PD-L1 status on prognosis was identified among the various breast cancer subtypes since only TNBC patients experience an improved prognosis compared to patients with luminal A tumors. Conversely, high infiltration by CD163 + cells is associated with worse prognosis only in patients with luminal A but not in TNBC tumors. Multivariate Cox regression analysis in TNBC patients revealed that increased CD8 + [hazard ratio (HR) = 0.542; 95% confidence interval (CI) 0.309-0.950; p = 0.032), CD8 + TCF1 + (HR = 0.280; 95% CI 0.101-0.779; p = 0.015), CD163 + PD-L1 + (HR: 0.312; 95% CI 0.112-0.870; p = 0.026) cells along with PD-L1 status employing two different scoring methods (HR: 0.362; 95% CI 0.162-0.812; p = 0.014 and HR: 0.395; 95% CI 0.176-0.884; p = 0.024) were independently linked with a lower relapse rate. Multivariate analysis in Luminal type A patients revealed that increased CD163 + was independently associated with a higher relapse rate (HR = 2.360; 95% CI 1.077-5.170; p = 0.032). This study demonstrates that the evaluation of the functional status of CD8 + T cells in combination with the analysis of immunosuppressive elements could provide clinically relevant information in different breast cancer subtypes.
(© 2024. The Author(s).)
Databáze: MEDLINE
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