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Introduction: To understand the immune system within the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC), it is crucial to elucidate the characteristics of molecules associated with T cell activation. Methods: We conducted an in-depth analysis using single-cell RNA sequencing data obtained from tissue samples of 19 NSCLC patients. T cells were classified based on the Tumor Proportion Score (TPS) within the tumor region, and molecular markers associated with activation and exhaustion were analyzed in T cells from high TPS areas. Results: Notably, tetraspanins CD81 and CD82, belonging to the tetraspanin protein family, were found to be expressed in activated T cells, particularly in cytotoxic T cells. These tetraspanins showed strong correlations with activation and exhaustion markers. In vitro experiments confirmed increased expression of CD81 and CD82 in IL-2-stimulated T cells. T cells were categorized into CD81highCD82high and CD81lowCD82low groups based on their expression levels, with CD81highCD82high T cells exhibiting elevated activation markers such as CD25 and CD69 compared to CD81lowCD82low T cells. This trend was consistent across CD3+, CD8+, and CD4+ T cell subsets. Moreover, CD81highCD82high T cells, when stimulated with anti-CD3, demonstrated enhanced secretion of cytokines such as IFN-g, TNF-a, and IL-2, along with an increase in the proportion of memory T cells. Bulk RNA sequencing results after sorting CD81highCD82high and CD81lowCD82low T cells consistently supported the roles of CD81 and CD82. Experiments with overexpressed CD81 and CD82 showed increased cytotoxicity against target cells. Discussion: These findings highlight the multifaceted roles of CD81 and CD82 in T cell activation, cytokine production, memory subset accumulation, and target cell cytolysis. Therefore, these findings suggest the potential of CD81 and CD82 as promising candidates for co-stimulatory molecules in immune therapeutic strategies for cancer treatment within the intricate TME. [ABSTRACT FROM AUTHOR]

Background: Sialic acid-binding Ig-like lectin-F (Siglec-F) in mice and its functional paralog Siglec-8 in humans are transmembrane receptors that play a role in the apoptosis of eosinophils. We aimed to evaluate the therapeutic potential of anti-Siglec-F antibodies in a murine model of allergic rhinitis. Methods: Twenty-eight BALB/c mice were used. In group A (control group, n = 7), mice were sensitized and challenged with saline. In group B (ovalbumin [OVA] challenge group, n = 7), OVA ivas used for i.p. sensitization and intranasal challenge. Mice in group C (control IgG group, n = 7) or those in group D (anti-Siglec-F group, n = 7) had been given rabbit control IgG or anti-Siglec-F antibody injections, respectively. We assessed the number of nose-scratching events; scrum total/OVA-specific IgE; the number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAD fluid; histopathological changes in nasal cavity tissues; and the levels of IL-4, IL-5, and IL-13 in BAL fluid. Results: Mice in group D had significantly less nose scratching. Serum total and OVA-specific IgE were not significantly changed. The number of eosinophils in BAL fluid and in the lamina propria of the nasal cavity mucosa was significantly decreased with anti-Siglec-F antibody treatment. The levels of Th2 cytokines such as IL-4, IL-5, and IL-13 were also significantly decreased with anti-Siglec-F antibody treatment. Conclusion: Anti-Siglec-F antibody has beneficial effects in a mouse model of experimental allergic rhinitis. [ABSTRACT FROM AUTHOR]