BACKGROUND: Currently, there is a lack of effective indicators for predicting the efficacy of immunotherapy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to investigate the expression and prognostic value of peripheral T lymphocyte subsets in advanced HCC.
METHODS: Patients with advanced HCC who were treated with immune checkpoint inhibitors (ICIs) from December 2021 to December 2023 were included in the study. Flow cytometry was used to detect lymphocyte subsets before treatment. The patients were divided into disease control (DC) and nondisease control (nDC) groups based on treatment efficacy. Relationships between the clinical characteristics/peripheral T lymphocytes and immunotherapy efficacy were analyzed. The effectiveness of peripheral T lymphocyte subsets in predicting immunotherapy efficacy for patients with advanced HCC was analyzed using receiver operating characteristic (ROC) curves.
RESULTS: A total of 40 eligible patients were included in this study. Non-DC was significantly associated with higher albumin-bilirubin (ALBI) scores. The percentages of γδ+Vδ2+PD1+ T cells and γδ+Vδ2+Tim3+ T cells were greater in the nDC group than in the DC group. Multivariable regression analysis revealed that the ALBI score and T lymphocytes expressing γδ+Vδ2+PD1+ and γδ+Vδ2+Tim3+ were founded to be independent influencing factors. The area under the ROC curve (AUC) values for these combinations was 0.944 (95% CI, 0.882 ~ 1.000).
CONCLUSIONS: The calculation of the ALBI score and determination of the percentages CD3+γδ+Vδ2+PD1+ T lymphocytes and CD3+γδ+Vδ2+Tim3+ T lymphocytes in the peripheral blood of patients with advanced HCC are helpful for predicting the patients\' responses to ICIs, helping to screen patients who may clinically benefit from immunotherapy. RETROSPECTIVELY REGISTERED: number: ChiCTR2400080409, date of registration: 2024-01-29.

The occurrence of colorectal cancer (CRC) is highly prevalent and severely affects human health, with the third-greatest occurrence and the second-greatest rate of death globally. Current CRC treatments, including surgery, radiotherapy, and chemotherapy, do not significantly improve CRC patients\' survival rate and quality of life, so it is essential to develop new treatment strategies. Adoptive cell therapy and other immunotherapy came into being. Currently, there has been an especially significant emphasis on γδ T cells as being the primary recipient of adoptive cell therapy. The present investigation found that γδ T cells possess the capability to trigger cytotoxicity in CRC cells, secrete cytokines, recruit immune cells for the purpose of destroying cancer cells, and inhibit the progress of CRC indirectly. Nevertheless, It is possible for γδ T cells to initiate a storm of inflammatory factors and inhibit the immune response to promote the advancement of CRC. This review demonstrates a close association between the γδ T cell initiation pathway and their close association with the intestinal flora. It has been observed that the intestinal flora performs a vital function in facilitating the stimulation and functioning of γδ T cells. The tumor-fighting effect is mainly regulated by desulphurizing Vibrio and lactic acid bacteria. In contrast, the regulation of tumor-promoting impact is closely related to Clostridia and ETBF. This review systematically combs γδ T cell dual function and their relationship to intestinal flora, which offers a conceptual framework for the γδ T cell application for CRC therapies.

UNASSIGNED: γδ T cells for tumor cell immunotherapy has recently become a hot topic.
UNASSIGNED: To investigate the stimulation of expanded γδ T cells in vitro to kill liver cancer cells and its mechanism, and in vivo validation.
UNASSIGNED: Peripheral blood mononuclear cells (PBMCs) were isolated and amplified. The proportion of γδ T cells in T cells was determined using flow cytometry. γδ T cells were selected as effector cells, and HepG2 cells as target cells in the cytotoxicity experiment. NKG2D blocker was used to block effector cells from identifying target cells, and PD98059 was used to block intracellular signaling pathways. The nude mice tumor model was established in two batches, the tumor growth curve was drawn, and the tumor formation effect was tested using small animal imager to verify the killing effect of γδ T cells.
UNASSIGNED: The γδ T cells in the three experimental groups exhibited a large amount of amplification (P < 0.01). In the killing experiment, the killing rate of γδ T cells stimulated by zoledronate (ZOL) in the experimental group was significantly higher than that in the HDMAPP group and the Mycobacterium tuberculosis H37Ra strain (Mtb-Hag) group (P < 0.05). The blocking effect of PD98059 is stronger than that of the NKG2D blocker (P < 0.05). Among them, in the HDMAPP group, when the target ratio was 40:1, the NKG2D blocker exhibited a significant blocking effect (P < 0.05). Alternatively, in the ZOL group, when the effect ratio was 10:1, the effector cells were blocked significantly after treatment using PD98059 (P < 0.05). In vivo experiments verified the killing effect of γδ T cells. According to the tumor growth curve, there was a difference between the experimental and control groups after cell treatment (P < 0.05).
UNASSIGNED: ZOL has high amplification efficiency and a positive effect on killing tumor cells.