HLA-G (Major Histocompatibility Complex, Class I, G)

This study represents the largest Italian cohort to date with comprehensive high-resolution HLA-G genotyping in LARC patients. Ongoing analyses aim to correlate these genetic findings with clinical parameters and HLA-G expression levels in liquid biopsies. This integrative approach may identify HLA-G-related genetic factors influencing prognosis, therapeutic response, and treatment-related adverse events in patients with LARC.

P1/2, N=31, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=117 --> 31

CD8 + T cells expressing ILT2 are overrepresented in patients with gastric adenocarcinoma, independent of PD-1 expression, and appear particularly susceptible to functional suppression in the presence of HLA-G-positive tumors. These findings highlight the immunomodulatory role of HLA-G in the tumor microenvironment and support its relevance as a potential target for personalized immunotherapeutic strategies.

In conclusion, this study highlights the increased expression of both HLA-G and KIR markers in CRC patients, suggesting their potential as prognostic and predictive markers. Our findings also suggest that HLA-G and KIR molecules could represent valuable therapeutic targets for future cancer immunotherapy strategies.

By simultaneously impairing tumor viability and reversing immune evasion, CBD-based compounds may enhance antitumor immunity and potentiate immunotherapy efficacy. Further research involving additional tumor cell lines, in vivo models, and immune-relevant systems are necessary to validate and expand upon these findings.

The fundic gland mucous neck cells were the only subpopulation that expressed HLA-G. Our findings, for the first time, suggest that fundic gland mucous neck cell HLA-G expression in PTTs is associated with GC progression.

While clinical correlations were not observed, likely due to limited sample size, these findings underscore the immunosuppressive role of MM-derived EVs. HLA-G+, PD-1+, and PD-L1+ EVs contribute to immune dysfunction in MM and represent promising targets to restore anti-tumor immunity.

The combination of niraparib with HLA-G blockade not only augmented NK cell-mediated tumor lysis in vitro but also synergistically inhibited tumor growth in humanized patient-derived xenograft models. Collectively, our results shed light on a previously unrecognized immune evasion mechanism and offer a compelling argument for the integration of HLA-G blockade with PARPi in cancer therapy.

We show original data on the HLA-C secretion via sEVs by early pregnancy EVT and confirm the production of HLA-G-positive sEVs. A new asset to the usefulness of the Sw71 spheroid model as an implanting blastocyst surrogate is added as a tool to elucidate the sEV-based signalization in the implantation.

These findings suggest that AFPGC employs multiple immune evasion mechanisms, notably through increased HLA-G expression and HLA-I deficiency, likely linked to its primitive cellular phenotype and reactivation of immunogenic oncofetal antigens. Such immune evasion features may underlie the aggressiveness of AFPGC and present promising targets for immunotherapeutic interventions.

JNJ-78306358 also blocked the interaction of HLA-G with its receptors in vitro, indicating that immune checkpoint blocking may contribute to its anti-tumor activity. These results suggest that T cell-redirection against HLA-G could be a potent and effective treatment for a wide range of solid tumor indications.

The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands, with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.