GZMH (Granzyme H)

ObjectivesThis retrospective study presents an integrative transcriptomic approach for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) by developing an immune response predictive score (IORPS) derived from tumor microenvironment (TME) transcriptomic profiles.MethodsA total of 30 R/M HNSCC patients treated with pembrolizumab or nivolumab, with available immune TME profiling data, were analyzed. The clinical relevance of IORPS was further validated using two external cohorts from the GEO database (CLB-IHN: GSE159067 and GHPS: GSE159141).ResultsBy comparing immune tumor microenvironment (TME) profiles between good and poor responders, GZMH, IFNG, and FASLG were identified as key DEGs with significantly higher expression in favorable immunotherapy responders. The IORPS, derived from transcriptomic profiling, demonstrated robust predictive accuracy for both immunotherapy response and survival outcomes in patients with R/M HNSCC.ConclusionCompared with the variable predictive performance of current biomarkers such as TPS and CPS, IORPS provides improved accuracy and reliability in identifying and stratifying patients most likely to benefit from immune checkpoint blockade therapy.

This study reveals variable expression of immune phenotypes in adult gliomas stratified by IDH status and characterizes immune compartment and genotype-dependent differences in the immunologic glioma landscape. These genotype-dependent, tumor and circulating immune ontogenies should guide future diagnostic and immunotherapeutic considerations in malignant glioma.

The model also achieved a F1-score of 0.76, an IoU of 0.63, and a mAP of 0.75, for the lymphocyte detection dataset demonstrating its effectiveness in detecting lymphocyte cells. To evaluate generalizability, we tested HVUNet on the MIDOG 2021 and PanopTILs datasets, observing competitive performance that demonstrated its robustness and broad applicability across diverse histopathology image analysis tasks.

FTL and PTP4A2 silencing could suppress the proliferation, migration and invasion abilities of HCC cells. This study identified eight prognostic gene signatures related to FGFBP2+ NK cell in HCC, which may serve as potential therapeutic targets for HCC.

Transcripts with higher m6A levels in the 3'UTR region were less abundant, and vice versa. However, changes in mRNA levels of the target genes didn't impact their corresponding protein levels or NK cell functionality.

This study identified key prognostic genes in AML and highlighted the critical role of NKT cells in AML pathogenesis. The study provides new insights and potential biomarkers for understanding AML biology, prognosis, and therapeutic targets.

RNA sequencing revealed that CD161neg T cells lacked the genes characteristic of mature MAIT cells including CCR6, CXCR6, ZBTB16, and IL18RAP, but expressed cytotoxic T cell-related genes GZMH and IFNG. This study shed new light on the heterogeneity and complexity of CD8αα+ T cells in MG patients with thymoma.

Patients underwent biopsy alone and received radiotherapy and temozolomide...This study provides insights into the potential of plasma omics features as biomarkers for glioblastoma diagnosis, progression and overall survival. Clinical implication should now be explored in dedicated prospective trials.

KG7, GZMH, and KLRB1 were identified as pivotal immune-related genes in ICI-MC. Biological enrichments included pathways involved in cell lysis, the CD8+ T-cell receptor pathway, natural killer cell-mediated cytotoxicity, RAGE signaling, and proinflammatory responses. The ceRNA network illuminated the role of critical molecules and underscored the importance of avoiding drugs such as acetohydroxamic acid in ICI treatment. Key message What is already known on this topic  Myocarditis is recognized as a serious ICI-associated toxicity, seemingly infrequent yet often fulminant and lethal. The underlying mechanisms of ICI-associated myocarditis remain not fully understood. Although the significance of T cells and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is evident, the inciting antigens, the reasons for their recognition, and the mechanisms causing cardiac cell injury are not well characterized. An improved understanding of ICI-associated myocarditis will provide insights into the equilibrium between the immune and cardiovascular systems. What this study adds  Our study further validates the significance of T cells and CTLA-4 in ICI-associated myocarditis. More importantly, we identified three genes-NKG7, GZMH, and KLRB1-essential for the development of ICI-MC and proposed ceRNA networks involving these three key genes. How this study might affect research, practice or policy  The newly discovered key genes and their intricate molecular interactions offer a comprehensive perspective on the mechanisms underlying ICI-MC. Furthermore, our findings advise caution regarding the use of drugs like acetohydroxamic acid during ICI treatment. As our understanding of these regulatory networks deepens, our study provides valuable insights that could inform future therapeutic strategies for ICI-MC.

The CD8+ T-cell-associated signature is expected to be a tool for optimizing individual patient decision-making and monitoring protocols, and to provide new ideas for treatment and prognostic assessment of HCC.

The study highlights the potential of specific cytokines and chemokines, in conjunction with TILs, as predictive biomarkers for pCR in patients with TNBC undergoing NAC. Further validation of these results is needed to elucidate their clinical relevance and potential for personalized therapeutic interventions in TNBC.

We established an immunocompetent humanized tumour model, providing a tool for immunotherapy research and defined effective anticancer activity of human effector CD8+ T cells with an activated and exhausted-like phenotype, supporting clinical exploration of such cells in adoptive T cell therapies.