Association between αβ and γδ T‑cell subsets and clinicopathological characteristics in patients with breast cancer

Abstract

The aim of the present study was to discuss the effect of surgery on the T-lymphocyte subsets of patients with breast cancer (BC) and investigate the association between peripheral blood αβ and γδ T-cell counts and the clinicopathological characteristics of BC. The CD3 + , CD4 + , CD8 + and γδ T-cell subsets in the peripheral blood of healthy volunteers and Patients with BC before and after surgery were determined using flow cytometry. The association between αβ and γδ T-cell counts in the peripheral blood and clinicopathological characteristics was analyzed by comparing the differences in the αβ and γδ T-cell counts in the peripheral blood of Patients with BC before and after surgery with those of healthy volunteers and combining with clinicopathological data. The CD3 + , CD4 + and γδ T-cell counts in the peripheral blood of Patients with BC were lower compared with those in healthy volunteers (P=0.0077, 0.0116 and 0.0003, respectively), whereas the number of CD8 + cells was higher (P=0.0241). The CD3 + , CD4 + and γδ T-cell counts and the CD4 + /CD8 + ratio after surgery were significantly higher compared with those before surgery (P=0.0109, 0.0031, 0.0165 and 0.018, respectively). There was no significant difference between the number of CD8 + cells before and after surgery (P=0.0053), but the number of CD8 + cells was higher in healthy volunteers compared with that in Patients with BC (P<0.05). Moreover, the CD3 + cell number was higher in patients with TNM stage II/III compared with those with TNM stage I disease (P=0.187 and 0.022, respectively), and the peripheral blood CD4 + /CD8 + ratio and number of γδ T cells were lower in stage III compared with stage I Patients with BC (P=0.0065 and 0.0176, respectively). Histological grading demonstrated that the CD4 + /CD8 + ratio and number of γδ T cells in patients with stage III BC were lower compared with those with stage I BC (P=0.02 and 0.0128, respectively). The γδ T-cell count in patients with luminal A and B subtypes was significantly higher compared with that in patients with basal-like subtype (P=0.004 and 0.0104, respectively). The CD3 + , CD4 + and γδ T-cell counts were significantly lower in patients with lymph node (LN) metastasis compared with those without LN metastasis, and the CD8 + cell number was lower in patients without LN metastasis compared with that in patients with >10 LN metastases (P=0.0086, 0.0000 and 0.00468, respectively). The CD8 + cell count in patients without LN metastasis was lower compared with that in patients with 4–9 and >10 LN metastases (P=0.0...

Study on the Killing Effect of γδT Cells Activated by Rukangyin on Breast Cancer MDA-MB-231 Cells

“…T cells are divided into αβT cells and γδT cells in accordance with different TCR types. γδT cells account for only 0.5 to 5% of adult peripheral blood [5,6], which are mainly distributed in mucosa and subcutaneous tissues and dominate an important role in antimicrobial, parasite, and tumor immunity [7][8][9][10][11][12][13]. In this study, rukangyin (RKY), zoledronic acid (ZOL), and phytohemagglutinin (PHA) of appropriate concentrations were used as stimulants to act on PBMC.…”

Breast Cancer Immune Landscape: Interplay Between Systemic and Local Immunity

“…According to studies involving multiple patient cohorts, BC is linked to a reduction in the number of 𝛾𝛿 T-cells. [156][157][158] The progression of BC, indicated by an increase in tumor size or involvement of regional lymph nodes, correlates with a decline in circulating 𝛾𝛿 T-cell counts. [157,159] Furthermore, 𝛾𝛿 T lymphocytes from BC patients were found to produce significantly higher levels of IL-6 and TNF-𝛼 but lower levels of IFN-𝛾 compared to healthy individuals.…”

“…[156][157][158] The progression of BC, indicated by an increase in tumor size or involvement of regional lymph nodes, correlates with a decline in circulating 𝛾𝛿 T-cell counts. [157,159] Furthermore, 𝛾𝛿 T lymphocytes from BC patients were found to produce significantly higher levels of IL-6 and TNF-𝛼 but lower levels of IFN-𝛾 compared to healthy individuals. They also exhibited a higher proportion of effector CD27 − cells relative to CD27 + memory cells.…”

Biological characteristics of γδT cells and application in tumor immunotherapy

“…Myeloid-derived suppressor cells inhibit the activation of CD8+T cells through high expression of ARG1 ( Romano et al, 2018 ; Sacchi et al, 2018 ), and reactive oxygen species (ROS) produced by neutrophils have a certain inhibitory effect on IL-17-producing γδT cells ( Wakita et al, 2010 ; Benevides et al, 2015 ; Coffelt et al, 2015 ). Other tumor-promoting effects of γδT cells include inhibiting the maturation of DCs, the senescent DCs can further suppress CD4+T cells and CD8+T cells ( Peng et al, 2007 ; Ye et al, 2013a ; Ye et al, 2013b ), inhibiting T cell responses by secreting galectin and expressing programmed cell death protein ligand 1 (PDL1); and inducing tumor cell proliferation by expressing IL-22 and biregulin ( Daley et al, 2016 ; Khosravi et al, 2018 ; Chen et al, 2019 ; Silva-Santos et al, 2019 ; Zhang et al, 2020 ). 7) Anti-tumor effect ( Figure 2 ): Direct anti-tumor effect: activated γδΤ cells can secrete perforin, granzyme B and IFN-γ or express CD95 ligand (CD95L) and TRAIL to directly kill tumor cells ( Gao et al, 2003 ); Indirect anti-tumor effect: Activated γδT cells induce DC maturation and infiltration by the secretion of TNF-α and IFN-γ ( Conti et al, 2005 ; Münz et al, 2005 ; Nussbaumer et al, 2011 ); induce robust NK cell-mediated anti-tumor cytotoxicity through CD137 engagement ( Maniar et al, 2010 ); efficiently processed and displayed antigens and provided co-stimulatory signals sufficient for strong induction of naïve αβT cell proliferation and differentiation ( Brandes et al, 2005 ; Khan et al, 2014 ; Mao et al, 2014 ); γδT cells can target tumor associated macrophages and MDSCs to improve their anti-tumor ability.…”