With the alarming surge in COVID-19 cases globally, vaccination must be prioritised to achieve herd immunity. Immune dysfunction is detected in the majority of patients with COVID-19; however, it remains unclear whether the immune responses elicited by COVID-19 vaccination function against the Omicron subvariant BA.2. Of the 508 enrolled patients infected with Omicron BA.2, 102 were unvaccinated controls, and 406 were vaccinated. Despite the presence of clinical symptoms in both groups, vaccination led to a significant decline in nausea or vomiting, abdominal pain, headache, pulmonary infection, and overall clinical symptoms and a moderate rise in body temperature. The individuals infected with Omicron BA.2 were also characterised by a mild increase in both serum pro- and anti-inflammatory cytokine levels after vaccination. There were no significant differences or trend changes between T- and B-lymphocyte subsets; however, a significant expansion of NK lymphocytes in COVID-19-vaccinated patients was observed. Moreover, the most effective CD16^brightCD56^dim subsets of NK cells showed increased functional capacities, as evidenced by a significantly greater IFN-γ secretion and a stronger cytotoxic potential in the patients infected with Omicron BA.2 after vaccination. Collectively, these results suggest that COVID-19 vaccination interventions promote the redistribution and activation of CD16^brightCD56^dim NK cell subsets against viral infections and that they could facilitate the clinical management of patients infected with Omicron BA.2.

Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4), an emerging immune checkpoint molecule, exhibits therapeutic potential in acute myeloid leukemia (AML). While single nucleotide polymorphisms (SNPs) of immune checkpoint genes have been extensively investigated in AML, the association between LILRB4 genetic polymorphisms and clinical outcomes remains unexplored. We investigated SNPs within the LILRB4 immunoglobulin domain and immunoreceptor tyrosine-based inhibitory motif regions in 151 AML patients and 203 controls. The rs1048801 G allele was significantly associated with increased LILRB4 mRNA expression, higher disease susceptibility, and reduced overall survival. Functional studies revealed that the G allele enhanced AML cell proliferation and colony formation. Furthermore, protein-protein interaction network analysis identified CD4 as a pivotal downstream mediator of LILRB4. Flow cytometry revealed elevated LILRB4 expression in CD45+ leukocytes and CD45+ CD33+ CD14+ monocytic AML cells from G allele carriers, concomitant with reduced CD3+ CD4+ T cell populations and impaired proliferation. Collectively, these findings establish rs1048801 as a critical modulator of AML progression through LILRB4-mediated CD4+ T cell suppression, providing new insights for personalized therapeutic strategies.

The human PYHIN family proteins, including AIM2, IFI16, IFIX, and MNDA, which are crucial cytosolic nucleic acid sensors. These proteins share a common structural feature, including signature N-terminal PYD domain and C-terminal HIN-200 domain, which enable them to recognize intracellular nucleic acids and assemble inflammasomes, triggering inflammatory responses and programmed cell death. Over the last decade, it has emerged that the PYHIN family proteins play multifaceted roles in cancer biology, with dualistic roles due to tumor heterogeneity and the tumor microenvironment’s plasticity through dependent or independent of inflammasome mechanisms. Here, we discuss their ability to function as both a tumor suppressor and a tumor promoter of tumor progression emphasizes the need for further research to delineate the precise mechanisms by which these proteins operate in various cancer contexts. Understanding these dynamics could pave the way for novel therapeutic approaches that harness the dual nature of PYHIN family members to improve cancer treatment outcomes.

With the alarming surge in COVID-19 cases globally, vaccination must be prioritised to achieve herd immunity. Immune dysfunction is detected in the majority of patients with COVID-19; however, it remains unclear whether the immune responses elicited by COVID-19 vaccination function against the Omicron subvariant BA.2. Of the 508 Omicron BA.2-infected patients enrolled, 102 were unvaccinated controls and 406 were vaccinated. Despite the presence of clinical symptoms in both groups, vaccination led to a significant decline in nausea or vomiting, abdominal pain, headache, pulmonary infection, overall clinical symptoms, and a moderate rise in body temperature. Omicron BA.2-infected individuals were also characterised by a mild increase in both serum pro- and anti-inflammatory cytokine levels after vaccination. There were no significant differences or trend changes between T and B lymphocyte subsets; however, a significant expansion of NK lymphocytes in COVID-19-vaccinated patients was observed. Moreover, the most effective CD16 ^bright CD56 ^dim subsets of NK cells showed increased functional capacities, as evidenced by a significantly greater IFN-γ secretion and stronger cytotoxic potential in Omicron BA.2-infected patients after vaccination. Collectively, these results suggest that COVID-19 vaccination interventions promote the redistribution and activation of CD16 ^bright CD56 ^dim NK cell subsets against viral infections, and could facilitate the clinical management of Omicron BA.2-infected patients.