CD39 identifies a specific CD8 + T cell population in lung adenocarcinoma-related metastatic pleural effusion.

Malignant pleural effusion (MPE), which is a complex microenvironment that contains numerous immune and tumour signals, is common in lung cancer. Gene alterations, such as driver gene mutations, are believed to affect the components of tumour immunity in the microenvironment (TIME) of non-small-cell lung cancer. In this study, we have shown that pleural CD39 + CD8 + T cells are selectively elevated in lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFRwt) compared to those with newly diagnosed mutant EGFR (EGFRmu). Furthermore, these CD39 + CD8 + T cells are more prevalent in MPE with acquired resistance to EGFR-tyrosine kinase inhibitors (AR-EGFR-TKIs). Our analysis reveals that pleural CD39 + CD8 + T cells exhibit an exhausted phenotype while still retaining cytolytic function. Additionally, they have a higher T cell receptor (TCR) repertoire clonality compared to CD39-CD8 + T cells, which is a unique characteristic of LUAD-related MPE. Further investigation has shown that TCR-Vß clonality tends to be more enhanced in pleural CD39 + CD8 + T cells from MPE with AR-EGFR-TKIs. In summary, we have identified a subset of CD8 + T cells expressing CD39 in MPE, which may potentially be tumour-reactive CD8 + T cells. This study provides new insights into the dynamic immune composition of the EGFRmu tumour microenvironment.

Combining local cryoablation with PD-L1 blockade synergistically eradicates established murine lung cancer by modulating mitochondrial in PD-1+CD8+ T cell.

Immune checkpoint blockade (ICB) has shown improvement in overall survival for lung cancer in clinical trials. However, monotherapies have limited efficacy in improving outcomes and benefit only a subset of patients. Combination therapies targeting multiple pathways can augment an immune response to improve survival further. Here, we demonstrate that combinatorial anti-PD-L1/cryoablation therapy generated a synergistic antitumor activity in the established lung cancer model. Importantly, it was observed that this favorable antitumor immune response comes predominantly from the PD-1+CD8+ T cells generated after the combination therapy, referred as improvement of IFN-γ production and mitochondrial metabolism, which resembled highly functional effectors CD8+ T cells. Notably, the cellular levels of mitochondrial reactive oxygen and mitochondria mass excessively coincided with alteration of IFN-γ secretion in PD-1+CD8+T cell subset. So far, anti-PD-L1/cryoablation therapy selectively derived the improvement of depolarized mitochondria in PD-1+CD8+T cell subset, subsequently rebuild the anti-tumor function of the exhausted CD8+ T cells. Collectively, there is considerable interest in anti-PD-L1 plus cryoablation combination therapy for patients with lung cancer, and defining the underlying mechanisms of the observed synergy.

Imbalance of Circulating Monocyte Subsets in Subjects with Newly Emerged and Recurrent Hospital-Acquired Pneumonia.

OBJECTIVE: Hospital-acquired pneumonia (HAP) is one of the most common diseases in the intensive care unit, where the development of disease is closely related with the host immune response. Monocytes play an important role in both innate and adaptive immune system. We aimed to investigate the changes of circulating monocyte subsets in subjects with HAP to explore its value in monitoring HAP. METHODS: In total, 60 HAP patients and 18 healthy individuals were enrolled in this study. Human monocyte subsets are classified into 3 groups: nonclassical (NC), intermediate (ITM), and classical (CL). Also, programmed death ligand 1 (PD-L1) expression on circulating monocyte subsets was measured by flow cytometry. RESULTS: Data showed that the ratio of NC, ITM, and CL among monocytes was comparable between HAP patients and healthy controls (P > .05). There was a remarkable imbalance of NC and CL in newly emerged HAP compared to healthy controls (P < .05), subsequently reaching normalization in recurrent HAP (P > .05). Furthermore, although PD-L1 was seemly constitutively expressed by NC, ITM, and CL groups regardless of disease status, it was noted that PD-L1 was dominantly expressed in the CL group (P < .05). CONCLUSION: Given distinct PD-L1 expression, a shift of CL/NC in newly emerged HAP would constitute an inhibitory anti-pathogen immune response. Normalization of circulating monocyte subsets on recurrence of HAP might be the consequence of immune memory of bacterial infection.

Identification of a gene engineering antibody against cystic echinococcosis in liver.

OBJECTIVE: To identify a gene engineering antibody against cystic echinococcosis in liver. METHODS: A single chain of variable fragment of human antibodies (ScFvs) was selected from the library by using affinity selection technique with the recombinant antigen on solid surface. The positive clones were demonstrated by ELISA and their DNA sequences were also determined. RESULTS: The DNA sequence data showed that the antibody gene is composed of 768 bp. In addition, a specific combination capacity with recombinant Echinococcus granulosus antigen B (r-EgB) was demonstrated by ELISA. CONCLUSION: The obtained gene engineering antibody against r-EgB may have potential implications in immunological treatment and drug targeting delivery.