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

Future research priorities include integrating AI-based immune profiling, precision genome editing, and advanced 3D-bioprinting technologies. Together, these innovations represent a paradigm shift toward developing safer, more effective, universally compatible stem cell therapies for diseases previously deemed untreatable.

Taken together, our study uncovers ICG signatures linked to tumor progression and sheds light on the complex network of microbiota-host immunity interactions within the lung microenvironment. This study lays the groundwork for future mechanistic studies and underscores the significance of microbiota-host immunity interactions for predicting and tracking the response to cancer treatment.

Our findings reveal regimen-specific systemic immune mechanisms in advanced HCC: Atez/Bev amplifies monocyte-NK cytotoxic axes, whereas Dur/Tre enhances monocyte-T cell inflammatory networks and TCR repertoire diversity. These insights highlight distinct predictive biomarkers and support regimen-tailored immunotherapy in HCC.

This study proved that inhibition USP2a could suppress tumor growth through two mechanisms: directly inhibiting tumor cell proliferation and remodel immune-cold microenvironment. Therefore, inhibiting USP2a could sensitize tumor to anti-PD-1 therapy.

Together, these findings suggest that proteasome inhibition could simultaneously boost both phases of the shock-and-kill strategy, by reactivating latent HIV-1 and by improving NK cell-mediated clearance through disruption of the NKG2A-HLA-E axis. This dual effect may significantly strengthen the "kill" phase of the shock-and-kill approach and could represent a promising path toward achieving a functional HIV-1 cure.

In this exploratory study, we analyzed CD73 expression and related immune markers during sequenced EGFR-TKI treatment, including osimertinib, to identify potential biomarkers for CD73-based therapeutic opportunities in EGFR-resistant tumors...We demonstrated differential expression patterns among the immune markers and higher levels of CD73 in cases with non-T790M-resistance to EGFR-TKIs. Although a limited number of cases were included in these analyses, the results might point to a potential role of immune markers inducing an immunosuppressive environment and thereby contribute to development of resistance to TKIs, which in turn could have future therapeutic implications.

Here, we demonstrate that NK cell suppression in the context of adenosine is most profound in NK cells homozygous for the V5 variant. Our results reveal a novel link between metabolism and immunologic inhibition and highlight the KLRC1-V5 variant as a putative biomarker for response to anti-NKG2A therapy and/or susceptibility to adenosine-driven immunosuppression.

The importance of the NKG2A: HLA-E immune checkpoint axis was established using both HLA-E knockout EBV+ LCL and antibody blockade of NKG2A which demonstrated enhanced NK-mediated cytotoxicity in the absence of NKG2A-HLA-E interactions. Taken together, our results support that NKG2A+ NK cells are educated and functionally cytotoxic against EBV-infected B cells and suggest therapeutics targeting the NKG2A: HLA-E immune checkpoint axis would be a good option for EBV-associated malignancies.

Understanding the role of HLA-E in tumor immune evasion provides valuable insights for developing novel personalized cancer immunotherapies. Targeting HLA-E has the potential to increase the effectiveness of current treatments and improve patient prognosis across diverse cancer types.

Concordantly, higher SP scores associated with lower risk of nasopharyngeal carcinoma and ulcerative colitis. Thus, the SP score may serve as a genetic tool to guide clinical NK cell intervention strategies, including therapeutic NKG2A blockade.

ILC1 from NV-HCC also displayed enhanced IL-2/IL-15 signaling and interactions with CD8 + T cells via HLA-E, suggestive of potential antitumor crosstalk. While our single-cell cohort size was limited, necessitating validation in larger datasets, our study reveals etiology-associated differences in ILC phenotypes in HCC and provides insight into their potential roles in modulating immune responses within the tumor microenvironment.