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Hepatocellular Carcinoma (HCC), the predominant primary hepatic malignancy, is the prime contributor to mortality. Despite the availability of multiple surgical interventions, patient outcomes remain suboptimal. Immunotherapies have emerged as effective strategies for HCC treatment with multiple clinical advantages. However, their curative efficacy is not always satisfactory, limited by the dysfunctional T cell status. Thus, there is a pressing need to discover novel potential biomarkers indicative of T cell exhaustion (Tex) for personalized immunotherapies. One promising target is Cyclin-dependent kinase inhibitor 2 (CDKN2) gene, a key cell cycle regulator with aberrant expression in HCC. However, its specific involvement remains unclear. Herein, we assessed the potential of CDKN2 expression as a promising biomarker for HCC progression, particularly for exhausted T cells. Our transcriptome analysis of CDKN2 in HCC revealed its significant role involving in HCC development. Remarkably, single-cell transcriptomic analysis revealed a notable correlation between CDKN2 expression, particularly CDKN2A, and Tex markers, which was further validated by a human cohort study using human HCC tissue microarray, highlighting CDKN2 expression as a potential biomarker for Tex within the intricate landscape of HCC progression. These findings provide novel perspectives that hold promise for addressing the unmet therapeutic need within HCC treatment. [BMB Reports 2024; 57(6): 287-292].

Study implicates lack of key hormone, battle-weary immune cells, and awakened viruses.

Response to protein complicates immunotherapy research.

COVID-19 variants of concern, including B.1.1.7, B.1.351, and P.1, encompass mutations facilitating immune evasion. Neutralizing antibody recognition and function may be variably impaired. We considered the impact of mutations on T cell responses. Mutations could be neutral or result in either loss or gain of predicted epitopes depending on HLA type., Competing Interests: Professors Altmann and Boyton have received remuneration for consultancies with Oxford ImmunoTec., (© 2021.)

An excess of exhausted T cells may explain why some patients with large B-cell lymphoma do not benefit from chimeric antigen receptor (CAR) T cells, a recent study concludes. The research also shows that patients with monocyte-like cells in their infusions are more likely to develop severe neurologic side effects. The study suggests measures to increase the effectiveness and safety of CAR T-cell products., (©2020 American Association for Cancer Research.)

In a phase I/II study, chimeric antigen receptor T cells produced complete remissions in 88% of patients with refractory or relapsed follicular lymphoma, all of whom remained in remission after a median of 2 years of follow-up. The treatment induced cytokine release syndrome and neurotoxicity in 50% of patients, but none developed side effects more severe than grade 2., (©2019 American Association for Cancer Research.)

Scientists have identified a wide variety of challenges preventing the development of effective CAR T-cell therapies for solid tumors, but they are investigating just as many potential solutions. Progress has been slow, but many researchers remain optimistic that successful CAR T-cell therapies, either alone or in combination with other treatments, will eventually be developed., (©2018 American Association for Cancer Research.)