HLA-G positive

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.

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.

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.

Interestingly, we found a higher CD4+HLA-G+ percentage in the group with unmutated immunoglobulin heavy chain variable region (IGHV) genes compared to the group with mutated IGHV gene after 48 h co-culture. In summary, increasing evidence has revealed that, in addition to HLA-G expressed on tumor cells, intercellular transfer of HLA-G among cancer cells and immune cells through trogocytosis plays important roles in mechanism of immune escape, disease progression and poor clinical outcome.

P1/2, N=3, Terminated, Hoffmann-La Roche | N=150 --> 3 | Trial completion date: Jan 2027 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Mar 2024; Sponsor decision (not related to safety, efficacy or quality).

P1/2, N=150, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

Conclusions The use of natural receptors ILT2 and ILT4 to target HLA-G takes advantage of the physiological pairing of the ILT receptors with the multiple immunosuppressive HLA-G isoforms thereby circumventing the possibility of antigen escape often observed in CAR-directed therapy. We demonstrated that engineered CIR-NK cells can convert HLA-G expression in AML from a potent inhibitor of leukocyte activity into a target for anti-tumor control.

As no significant differences were found between the GC assessed stages in our study population, we suggest that sHLA-G is not an adequate marker for staging GC, but it does have diagnostic potential. In addition to providing information on the potential of sHLA-G as a diagnostic marker for GC, our study demonstrate that HLA-G molecules can be found in the membrane of exosomes, which highlights the need to perform studies with a larger number of samples to explore the functional implications of HLA-G positive exosomes in the context of gastric cancer, and to determine the clinical significance and possible applications of these findings in the development of non-invasive diagnostic methods.

P1/2, N=150, Recruiting, Hoffmann-La Roche | Not yet recruiting --> Recruiting