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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Vydáno v:	Cell reports. Medicine Ročník 6; číslo 8; s. 102252
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 19.08.2025 Elsevier
Témata:	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
On-line přístup:	Získat plný text
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2666-3791 2666-3791
DOI:	10.1016/j.xcrm.2025.102252