The discovery of prognostic biomarkers has provided doctors the ability to determine likelihood of future clinical events, disease recurrence, or disease progression in a given patient population. These tools are also extremely useful in determining the proper treatment course for a patient, and in breast cancer, could offer investigators a way to determine which patients could avoid chemotherapy and receive a less aggressive therapy.
Specifically, it has been found that tumor-infiltrating lymphocytes (TILs) at baseline is an independent, positive prognostic marker in HER2+ early breast cancer patients treated with trastuzumab and pertuzumab-based neoadjuvant chemotherapy. Depending on the characteristics of their receptors, TILs are characterized in αβ and γδ T cells, although the latter are poorly represented in blood, they rapidly expand in response to tumor. Furthermore, specific γδ T cell subsets have been associated with remission and improved overall survival of patients with triple-negative breast cancer, but little is known about circulating αβ and γδ T cells in patients treated with trastuzumab + pertuzumab.
Recently, our PHERGain study demonstrated that early F-FDG-PET assessment might be a useful tool in identifying HER2+ early breast cancer patients who achieved a pathological complete response through a chemotherapy-free regimen of trastuzumab and pertuzumab. Utilizing the samples from this trial, the LINGain trial aims to investigate longitudinal changes in the proportion, activation, and apoptosis of circulating αβ and γδ T cell subsets in a cohort
of patients with HER2+ early breast cancer.
The trial included 24 patients from the cohort B of PHERGain and 48 healthy donors as control from 10 site across Spain. Blood samples were collected before starting the treatment, and again at the end of the second cycle. Comparison was made to the healthy samples by flow cytometry analysis, detecting specific surface markers on blood mononuclear cells.
Results were shared at the San Antonio Breast Cancer Symposium 2021. The analysis revealed that after treatment the absolute count of both γδ and αβ T cells were decreasing, but surprisingly the number of cells undergoing apoptosis (cell-death) was augmenting after 2 cycles of neoadjuvant treatment with respect to the initial number in HER2+ early breast cancer patients. Moreover, a significantly higher fraction of γδ TEMRA than αβ TEMRA (T effector memory cells re-expressing CD45RA) was observed in CD3+ and CD3+CD8+ T cell subsets, meaning that γδ T cells were in their functional stage, and thus properly acting against the tumor.
“To our knowledge, LINGain is the first study to assess the evolution of peripheral αβ and γδ T cells in the context of neoadjuvant chemotherapy-free regimen with trastuzumab and pertuzumab in HER2[+] EBC patients. Although no evidence of T cell association with clinical characteristics was found, we need to keep investigating in this direction, to uncover the role and the prognostic value of the innate immune system in the context of HER2 blockade strategies”, concluded Dr. Llombart-Cussac, PI of the study.
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