Tumor-specific CD8 T cell characterization in HR+ breast cancer reveals an impaired antitumoral response in patients with lymph node metastasis

Most breast cancers express the estrogen receptor (ER), but the immune response of hormone receptor-positive (HR+) breast cancer remains poorly characterized. Here, dendritic cells loaded with tumor lysate are used to identify tumor-reactive CD8 T cells, which are detected in most HR+ breast cancer...

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Bibliographic Details
Published in:Cell reports. Medicine Vol. 6; no. 8; p. 102252
Main Authors: Pinho, Mariana Pereira, Antoun, Elie, Sandhar, Balraj, Shu, Ting, Gao, Fei, Yang, Xiaobao, Bates, Adam, Cerundolo, Lucia, Hamid, Megat H.B.A., Maldonado-Perez, David, Teague, Renuka, Warner, Eve, Winter, Lucinda, Alham, Nasullah Khalid, Verrill, Clare, Lord, Simon R., Rostron, Timothy, Clark, Sally-Ann, Waugh, Craig, Sopp, Paul, Conlon, Chris, Fernandes, Ricardo A., Harris, Adrian L., Peng, Yanchun, Adwani, Asha, Dong, Tao
Format: Journal Article
Language:English
Published: United States Elsevier Inc 19.08.2025
Elsevier
Subjects:
Advanced Basic Science
antitumor CD8 T cells
Breast Neoplasms - immunology
Breast Neoplasms - pathology
cancer testis antigen
CD8-Positive T-Lymphocytes - immunology
CDR3
CTA
Dendritic Cells - immunology
ER+ breast cancer
Female
Humans
Lymph Nodes - pathology
Lymphatic Metastasis - immunology
Lymphocytes, Tumor-Infiltrating - immunology
metastatic luminal breast cancer
Middle Aged
moDC
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
Receptors, Estrogen - metabolism
T cell receptor
T cell repertoire
tumor lysate
tumor-specific T cells
tumor lysate
ER+ breast cancer
CTA
moDC
T cell receptor
T cell repertoire
metastatic luminal breast cancer
tumor-specific T cells
antitumor CD8 T cells
CDR3
cancer testis antigen
ISSN:2666-3791, 2666-3791
Online Access:Get full text
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Summary:Most breast cancers express the estrogen receptor (ER), but the immune response of hormone receptor-positive (HR+) breast cancer remains poorly characterized. Here, dendritic cells loaded with tumor lysate are used to identify tumor-reactive CD8 T cells, which are detected in most HR+ breast cancer patients, especially those with early-stage tumors. When present, the circulating antitumor CD8 response contains cytotoxic T cells with diverse specificity and T cell receptor (TCR) repertoire. Additionally, patients with blood cancer-specific T cells have significantly more CD8 tumor-infiltrating lymphocytes (TILs). Moreover, tumor-reactive TCR sequences are detected in the tumor, but at a significantly lower proportion in patients with lymph node involvement. Our data suggest that HR+ breast cancer patients with lymph node metastasis lack tumor-specific CD8 T cells with capacity to infiltrate the tumor at significant levels. However, early-stage patients have a diverse antitumor CD8 response that could be harnessed to develop immunotherapeutic approaches for late-stage HR+ patients. [Display omitted] •Antitumor CD8 T cells are detected in patients with early-stage breast cancer•When present, the tumor-reactive blood CD8 T cell repertoire is highly diverse•Presence of circulating tumor-reactive T cells correlates with CD8 TIL abundance•Patients with lymph node metastasis have lower frequency of tumor-reactive TILs Pinho et al. show that HR+ breast cancer patients with lymph node metastasis have an impaired antitumor CD8 immune response, with less frequency of tumor-reactive TILs. Yet, early-stage patients exhibit a diverse tumor-reactive CD8 T cell repertoire that could be harnessed to develop immunotherapeutic interventions for late-stage HR+ patients.
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ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2025.102252