Immunobiology最新文献

Objective: Hepatocellular carcinoma (HCC) exhibits a profoundly immunosuppressive microenvironment that limits the efficacy of current immunotherapies. This study evaluated the antitumor activity of unmodified γδ T cells in HCC and defined immune checkpoint-mediated mechanisms that restrict their therapeutic durability.

Methods: Bioinformatic analyses of LIHC datasets were performed to identify candidate prognostic T-cell receptor γ variable (TRGV) genes. Ex vivo-expanded γδ T cells were evaluated using in vitro co-culture assays with PD-L1-low (Huh7) and PD-L1-high (HCC-LM3) HCC cell lines, real-time cytotoxicity analyses, and cytokine profiling. Therapeutic efficacy, immune checkpoint regulation, and systemic safety were further assessed in subcutaneous xenograft mouse models using co-implantation and intravenous administration strategies.

Results: TRGV3 expression correlated with improved overall survival and reflected γδ T-cell presence within the tumor microenvironment. Unmodified γδ T cells exerted potent, dose-dependent cytotoxicity against HCC cells and suppressed tumor growth in vivo, particularly in PD-L1-negative models. In PD-L1-positive HCC-LM3 tumors, γδ T cell efficacy was reduced following systemic administration and was associated with tumor-induced PD-L1 upregulation, delayed cytotoxicity, and tumor recurrence. Blockade of the PD-L1/PD-1 axis restored durable γδ T cell-mediated tumor control. Importantly, γδ T-cell treatment was well tolerated, with no overt systemic toxicity observed.

Conclusion: Unmodified γδ T cells demonstrate strong antitumor activity and a favorable safety profile in HCC but are limited by adaptive PD-L1-mediated immune resistance in PD-L1-positive tumors. These findings provide a mechanistic rationale for combining γδ T cell-based therapies with immune checkpoint inhibition to enhance therapeutic efficacy in advanced HCC.

Background: Neurocysticercosis (NCC) is a parasitic infection of the central nervous system (CNS) caused by the larval form of Taenia solium. This disease provokes an inflammatory response that intensifies when the parasite dies. This study aimed to assess the expression of the cytokines IL-10, IL-1β, and TGF-β in primary astrocyte cultures derived from rat brains at 5 and 14 days in vitro (DIV) following exposure to T. solium cysticercus antigens.

Methods: Primary astrocyte cultures obtained from 3-day-old postnatal rats were incubated for 24 h with either Excretory/Secretory (E/S) antigens or Total antigen (Tag), while lipopolysaccharide (LPS) was used as a positive control. Cytokine expression (IL-10, IL-1β, and TGF-β1) was quantified by RT-qPCR.

Results: DIV5 culture contains astrocytes and neurons, while in DIV14 only astrocytes were detected. At DIV5, the incubation with E/S products increased the gene expression of IL-10 and IL-1β. Conversely,at DIV14, E/S antigens only augmented IL-10 mRNA levels. Moreover, Tag did not change IL-10, IL-1β, and TGF-β gene expression in both DIV5 and DIV14 cultures. Finally, TGF-β expression remains unchanged after T. solium antigen exposure.

Conclusions: T. solium E/S products may differentially modulate astrocyte cytokine responses in a stage-dependent manner. In addition, the Tag obtained from viable cysts does not affect the studied cytokine gene expression. These results underscore the potential role of astrocytes in the neuroinflammatory processes associated with NCC.

Objective: This study investigates the clinical utility of circulating tumor cells (CTCs) in combination with serum tumor markers/inflammatory cytokines for the diagnosis of early-stage non-small cell lung cancer (NSCLC).

Methods: A retrospective analysis was conducted on the clinical data of 43 NSCLC patients (stage I-IIA) who underwent surgical treatment at the Fourth Hospital of Hebei Medical University between November 2021 and December 2022. A control group of 50 healthy individuals was also included. Comparative analyses of CTCs, serum tumor markers, and inflammatory cytokine levels were performed between the two groups. The clinical diagnostic value was assessed using receiver operating characteristic (ROC) curve analysis.

Results: The median concentrations of CTCs, carcinoembryonic antigen (CEA), Cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and interleukin-17 A (IL-17 A) were significantly elevated in the NSCLC cohort compared to the healthy control cohort, while interleukin-2 (IL-2) levels were reduced (P < 0.05). ROC curve analysis revealed that CTCs exhibited a sensitivity of 65.12%, specificity of 100.00%, and an area under the curve (AUC) of 0.826 for the diagnosis of early-stage NSCLC. The combined diagnostic sensitivity of CTCs, CEA, CYFRA21-1, and NSE reached 86.05%, with 100.00% specificity and an AUC of 0.945. Among the seven inflammatory cytokines evaluated, IL-17 A exhibited the highest diagnostic efficacy for early-stage NSCLC, with an AUC of 0.871, sensitivity of 93.02%, and specificity of 75.00%. The combination of IL-17 A and CTCs achieved an AUC of 0.953, with a sensitivity of 86.05% and specificity of 90.00%.

Conclusion: The integration of CTCs with serum tumor markers and/or inflammatory cytokines provides high sensitivity and specificity for the diagnosis of early-stage NSCLC, highlighting its significant clinical potential.