CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer

Abstract

Background: Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8 + memory T cell subsets including T stem cell memory (TSCM) in tumor-draining lymph nodes of patients with breast cancer (BC). Methods: Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with BC and stained for CD8, CCR7, CD45RO, CD95 markers to detect different subtypes of memory cells in the CD8 + lymphocyte population. Data were acquired on four-color flow cytometer and analyzed with CellQuest Pro software. Results: We observed that 47.65 ± 2.66% of CD8 + lymphocytes expressed the CD45RO, a marker for memory T cells. Statistical analysis showed that the total frequency of central memory T cells (TCM) and their subset with low CD45RO expression was significantly higher in tumor-involved nodes compared to tumor-free ones (P = 0.024 and P = 0.017, respectively). The level of CD95 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45RO hi and CD45RO low subsets, and TSCM was higher in patients with stage II compared to those in stage I (P < 0.05). In addition, the percentage of naive CD8 + T cells was significantly lower in tumor-involved lymph nodes compared to tumor-free ones (P = 0.025). Conclusions: Our data collectively indicate no significant differences in the frequencies of CD8 + lymphocytes or their memory subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45 low TCM was higher in tumor-involved nodes. Along with a decrease in the frequency of naive T cells, the higher frequency of CD45 low TCM suggests that despite the immune reaction to provide a pool of effective memory cells, it is blocked in early-stage of memory cells' differentiation (CD45RO low), probably by tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer.

Counterbalance of Foxp3 and IDO expression at different tumor stages in aggressive breast cancer subtypes

“…In this study CD45R0+ cells were found in most of the tumor samples with CD8+ lymphocytes, suggesting that these TILs could be memory CTL (CD8+CD45R0+). In agreement with these results, Vahidi et al (2020) reported an increased frequency of CD8+CD45R0+ lymphocytes associated with large tumor size [49]. Furthermore, it has been reported that CD45R0 and CD8 expression and differentiation in immune cells parallelly increase in patients with BC malignant features such as advanced TS, poorly differentiated tumors and high number of nodes involved, as it was observed in this study.…”

“…Furthermore, it has been reported that CD45R0 and CD8 expression and differentiation in immune cells parallelly increase in patients with BC malignant features such as advanced TS, poorly differentiated tumors and high number of nodes involved, as it was observed in this study. It would suggest that, despite the efforts of the immune system to provide an effective response to eradicate the tumor, it is often functionally impaired as a result of interaction with, or signals from, transformed cells and the tumor microenvironment [49]. These interactions and signals can lead to transcriptional, functional, and phenotypic changes that diminish their ability to eradicate the tumor [28].…”

Immunotherapeutic Potential of T Memory Stem Cells

“…However, whether it is traditional immune cell therapy or new CAR-T cells and T-cell receptor T cells (TCR-T) therapy, all are based on terminally differentiated effector T (T TE ) cells, making it difficult to exert long-lasting anti-tumor effects in the body (8). Adoptive T cell therapy (ACT) is the in vitro expansion and reinfusion of tumorreactive T cells, and is a potential treatment method for the treatment of advanced cancer (9)(10)(11)(12)(13)(14). In infections and cancers, T lymphocytes expand and differentiate into effector cells and memory cells that clear pathogens.…”

Comprehensive analysis of the cancer driver genes in breast cancer demonstrates their roles in cancer prognosis and tumor microenvironment

“…For example, Rizeq’s study found that activation of the C–C chemokine receptor 7 (CCR7)-related complex increased tumor cell proliferation and migration [ 38 ]. Vahidi’s study concluded that CD8-positive memory T cells in tumor-draining lymph nodes are associated with CCR7 [ 39 ]. We found the specific expression and prognostic value of CCR7 in breast cancer.…”