BACKGROUND: One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment. METHODS: Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed. RESULTS: The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)]. CONCLUSIONS In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Hepatitis A Virus Cellular Receptor 2/immunology* ; Tumor Microenvironment/immunology* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Aged ; Adult ; Programmed Cell Death 1 Receptor/metabolism* ; Immunotherapy ; Clinical Relevance

Objective To compare the survival rates from two conservative strategies in the treatment of malignant pleural mesothelioma (pemetrexed plus cisplatin or pemetrexed plus carboplatin ).Methods Seventeen cases diagnosed of malignant pleural mesothelioma at clinical stages of or over Butchart Ⅲ in our hospital during 2005 -2009 were treated with pemetrexed plus cisplatin (10 cases,Group A)or pemetrexed plus carboplatin (7 cases,Group B ).The difference in the survival rates between these two groups was compared.Results The early survival rate (0 -3 months)in pemetrexed plus cisplatin (group A)-treated group was more than that of pemetrexed plus carboplatin group (group B),but the difference was not statistically significant (x2 =0,1.52,1.52,respectively,P ＞ 0.05 ).For the medium-term survival rate (4 - 9 months),group A was better than group B,and the difference was statistically significant( x2 =5.21,4.41,4.41,4.50,4.50,4.55,respectively,P ＜ 0.05 ).The two groups produced comparable long-term survival rate s (10 -12months) ( x2 =1.31,0.09,0.09,respectively,P ＞ 0.05 ).Conclusion To increase the medium-term survival rate (4 -9 months)of patients with MPM,we prefer to using pemetrexed plus cisplatin regime.For the patients with more severe side effects which can be relieved by folic acid and VitB12,this regime is also recommended.Otherwise,for the patients with unrelievable side effects,especially for those with poor physical condition or a short survival expectation,pemetrexed plus carboplatin is suggested.