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The immunohistochemical analysis was used to evaluate the expression of PD-L1 in 109 non-small cell lung cancer (NSCLC) tissues and para-tumor tissues. Associations between expressed PD-L1 and tumor histological types, degree of differentiation, and lymph node metastasis were calculated, and overall survival was assessed. Meanwhile, immunohistochemistry and immunofluorescence double labeling technique were performed to detect the expressions of PD-L1, CD1α, and CD83 on TIDC of 20 lung cancer tissues, and the expression of PD-L1 in CD1α+DCs and CD83+DCs and their significances were also explored. We found that the expression rate of PD-L1 in NSCLC was associated with histological types and overall survival. Patients with either adenocarcinoma or survival time after surgery less than 3 years showed higher expression rate of PD-L1. Furthermore, Cox model analysis indicated that PD-L1 might be regarded as a poor prognostic factor. PD-L1 could be also detected in CD1α+ immature DC in NSCLC, indicating that as a class of key anti-tumor immunocyte in tumor microenvironment, DC expressing PD-L1 itself might play an important role in keeping its immature status and contributing to tumor cells immune escape and disease progression.

Negative regulation of the signal mediated by the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway can effectively inhibit the function of T and B cells, which play a key role in the regulation of immune response. Recently, emerging evidence has suggested that the expression of PD-L1 is related to the mutation status of the epidermal growth factor receptor (EGFR). Moreover, the activation of the EGFR signaling pathway can induce expression of PD-L1. In the present study, we demonstrated that activated EGFR can upregulate the expression of PD-L1 through the interleukin 6/Janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) signaling pathway in non-small cell lung cancer (NSCLC) cells. Cells treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can downregulate the activation of the IL-6/JAK/STAT3 pathway, which subsequently reduces the expression of PD-L1. Furthermore, silencing of PD-L1 expression in NSCLC cells correlated with inhibition of cell proliferation and enhanced tumor cell apoptosis. In summary, our research indicates that EGFR is involved in the regulation of PD-L1 expression and cell proliferation via the IL-6/JAK/STAT3 signaling pathway in NSCLC. The present study suggests the potential of combined targeted therapy with immunotherapy in the treatment of NSCLC.

Background Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. Methods From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. Results Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. Conclusions LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Up-regulated PD-L1 expression in NSCLC is related to the degree of tumor cell differentiation and TNM stage. PD-L1 status may be a new predictor of prognosis for patients with NSCLC.

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Abstract:Cancer immunotherapy has produced impressive clinical results in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1), a large portion of cancer patients have not yet benefited from this novel therapy. T cell immunoglobulin and mucin domain 3 (TIM-3) has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy. Despite a large amount of experimental data showing an immune suppressive function of TIM-3 in vivo, the exact mechanisms are not well understood. To enable effective targeting of TIM-3 for tumor immunotherapy, further in-depth mechanistic studies are warranted. These studies will also provide much-needed insight for the rational design of novel combination therapy with other checkpoint blockers. In this review, we summarize key evidence supporting an immune regulatory role of TIM-3 and discuss possible mechanisms of action.