scholarly journals Selective Depletion of Regulatory T Cell Subsets by Docetaxel Treatment in Patients with Nonsmall Cell Lung Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Jie-Yao Li ◽  
Xiu-Fang Duan ◽  
Li-Ping Wang ◽  
Yu-Jie Xu ◽  
Lan Huang ◽  
...  

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 vitroassay 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.

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Zhang Nan ◽  
Wang Guoqing ◽  
Yu Xiaoxu ◽  
Mi Yin ◽  
He Xin ◽  
...  

Background. Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer, and the majority of NSCLC patients are diagnosed at the advanced stage. Chemotherapy is still the main treatment at present, and the overall prognosis is poor. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs) as the representative have been extensively applied for treating various types of cancers. Tumor mutation burden (TMB) as a potential biomarker is used to screen appropriate patients for treatment of ICIs. To verify the predictive efficacy of TMB, a systematic review and meta-analysis were conducted to explore the association between TMB and ICIs. Method. PubMed, EMBASE, Cochrane Library, and son on were systematically searched from inception to April 2020. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were estimated. Results. A total of 11 studies consisting of 1525 nonsmall cell lung cancer (NSCLC) patients were included. Comparison of high and low TMB: pooled HRs for OS, 0.57 (95% CI 0.32 to 0.99; P = 0.046 ); PFS, 0.48 (95% CI 0.33 to 0.69; P < 0.001 ); ORR, 3.15 (95% CI 2.29 to 4.33; P < 0.001 ). Subgroup analysis values: pooled HRs for OS, 0.75 (95% CI 0.29 to 1.92, P = 0.548 ) for blood TMB (bTMB), 0.44 (95% CI 0.26 to 0.75, P = 0.003 ) for tissue TMB (tTMB); for PFS, 0.54 (95% CI 0.29 to 0.98, P = 0.044 ) and 0.43 (95% CI 0.26 to 0.71, P = 0.001 ), respectively. Conclusions. These findings imply that NSCLC patients with high TMB possess significant clinical benefits from ICIs compared to those with low TMB. As opposed to bTMB, tTMB was thought more appropriate for stratifying NSCLC patients for ICI treatment.


Medicine ◽  
2017 ◽  
Vol 96 (6) ◽  
pp. e6087 ◽  
Author(s):  
Taro Koba ◽  
Takashi Kijima ◽  
Takayuki Takimoto ◽  
Haruhiko Hirata ◽  
Yujiro Naito ◽  
...  

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