Effector Mechanisms of CD8+ HLA-DR+ T Cells in Breast Cancer Patients Who Respond to Neoadjuvant Chemotherapy
| Autor: | Rubén Osuna-Gómez, Cristina Arqueros, Carla Galano, Maria Mulet, Carlos Zamora, Agustí Barnadas, Silvia Vidal |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Cancers, Vol 13, Iss 6167, p 6167 (2021) Cancers; Volume 13; Issue 24; Pages: 6167 Cancers r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau Universidad Europea (UEM) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| ISSN: | 2072-6694 |
| Popis: | Simple Summary This study contributes to the characterization of CD8+ HLA-DR+ T cell mediated-mechanisms involved in the anti-tumor response in breast cancer patients who respond to neoadyuvant chemotherapy (NACT). Cultures with plasma from responder (R), but not from non-responder (NR), patients increased the intracellular production of cytotoxic molecules and pro-inflammatory cytokines in CD8+HLA-DR+ T cells. However, the addition of neutralizing anti-IFN-gamma or anti-IL-12 antibodies to cultures with plasma from R patients decreased this effector function on CD8+HLA-DR+ T cells. These results suggest the presence of soluble factors in the plasma of R patients inducing the effector function of CD8+HLA-DR+ T cells. Cytotoxic T lymphocyte (CTLs) activation is an independent predictor of response to neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients. Here, we go deeper into the function of CD8+ HLA-DR+ T cells from NACT treated HER2 negative BC patients. Flow cytometry analysis revealed that CD8+ HLA-DR+ T cell percentage was increased in NACT responder (R) compared to non-responder (NR) patients. R patients with ER-/PR- hormone receptors had the highest CD8+ HLA-DR+ T cell frequencies, while no differences were found when patients were classified according to cancer stage or menopause status. Interestingly, the cytotoxicity and production of anti-tumor cytokines were enhanced when CD8+ HLA-DR+ T cells from healthy donors were cultured with plasma from R, but not from NR patients. The induced anti-tumor profile of CD8+ HLA-DR+ T cells was associated with plasmatic IL-12 and IFN-gamma levels, increased cytokines in R patients. IL-12 or IFN-gamma neutralization decreased cytotoxic activity and TNF-alpha production by cultured CD8+ HLA-DR+ T cells in R plasma presence. All these data suggest that an effective response to NACT in BC patients is associated with increased IL-12 or IFN-gamma levels involved in the induction of cytotoxic and pro-inflammatory mechanisms in CD8+ HLA-DR+ T cells. |
| Databáze: | OpenAIRE |
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