Abstract
Regulatory T (Treg) cells are potent suppressors that maintain immune homeostasis. Accumulation of Treg can inhibit effective immune responses in cancer patients, leading to tumor development and progression. Despite direct cytotoxicity, several chemotherapeutic drugs have been reported to deplete Treg cells for better prognosis for cancer patients. Treg cells are a heterogenous population with at least three different subsets, nonsuppressive, resting, and activated Treg cells. However, the characteristics of Treg cell subsets in lung cancer patients and how chemotherapy affects Treg cells remain elusive. In this study, we first analyzed Treg cell subsets in peripheral blood samples from 40 nonsmall cell lung cancer (NSCLC) patients and 20 healthy donors. Treg cells, specifically activated Treg cell subset, significantly increased in patients with NSCLC. Compared to nonsuppressive Treg cells, activated Treg cells expressed higher level of CD39 and predominantly produced inhibitory cytokines. In vitro assay showed that docetaxel reduced all three subsets of Treg cells. More importantly, we found docetaxel-based chemotherapy significantly decreased all three Treg subsets after 4 cycles of treatment in 17 NSCLC patients. Taken together, this study revealed dynamic changes of various Treg cell subsets in NSCLC patients before and after chemotherapy, providing activated Treg cells as a potential target for chemotherapy.
Highlights
Regulatory T cells (Treg cells) are a key member to maintain self-tolerance and immune homeostasis [1, 2]
The combination of Foxp3 and CD45RA staining of CD4+ T cells in peripheral blood mononuclear cells (PBMCs) of nonsmall cell lung cancer (NSCLC) patients revealed the existence of three subsets of Treg cells (Figure 1(a))
Our data showed that only activated Treg cells (aTreg) cells but not resting Treg cells (rTreg) or non-Treg cells increased in NSCLC patients compared to healthy donors (1.07 ± 0.16% versus 0.25 ± 0.04%, P < 0.001), indicating that aTreg cells might play an important role in the pathogenesis of lung cancer
Summary
Regulatory T cells (Treg cells) are a key member to maintain self-tolerance and immune homeostasis [1, 2]. They play crucial roles in a variety of human diseases, such as autoimmune disease, allergy, chronic infection, and cancers [3,4,5,6]. Treg cells can suppress the immune response of CD4+ and CD8+ T cells mainly by secretion of inhibitory cytokines such as interleukin (IL)-10 and transforming growth factorβ (TGF-β) [7, 8]. Sakaguchi’s group confirmed that human CD4+Foxp3+ Treg cells can be divided into three subsets: CD45RA+Foxp3lo, CD45RA−Foxp3hi, and CD45RA−Foxp3lo cells [12]. CD4+CD45RA−Foxp3lo Treg cells include a remarkable amount of nonregulatory, cytokine-secreting T cells (nonsuppressive T cells or non-Treg cells) [13,14,15]
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