CD8⁺T cell exhaustion is a state of T cell dysfunction during chronic infection and tumor progression. Exhausted CD8⁺T cells are characterized by low effector function, high expression of inhibitory receptors, unique metabolic patterns, and altered transcriptional profiles. Recently, advances in understanding and interfering with the regulatory mechanisms associated with T cell exhaustion in tumor immunotherapy have brought greater attention to the field. Therefore, we emphasize the typical features and related mechanisms of CD8⁺T cell exhaustion and particularly the potential for its reversal, which has clinical implications for immunotherapy.

Lymphocyte-specific protein tyrosine kinase (LCK) is common in a variety of hematologic malignancies but comparatively less common in solid tumors. This study aimed to explore the potential diagnostic and prognostic value of LCK across tumors through integrative and comprehensive pan-cancer analysis, as well as experimental validation. Multiple databases were used to explore the expression, alteration, prognostic value, association with immune infiltration, and potential functional pathways of LCK in pan-cancers. The results were further validated by western blotting and qPCR of patient samples as well as tumor cell lines. High LCK expression typically represents a better prognosis. Notably, drug sensitivity prediction of LCK identified P-529 as a candidate for drug development. Gene Annotations (GO) and KEGG analyses showed significant enrichment of PD-L1 and the T-cell receptor pathway. The results from patient samples and tumor cell lines confirmed these conclusions in LIHC. In conclusion, LCK is differentially expressed in multiple tumors and normal tissues. Further analysis highlighted its association with prognostic implications, pan-cancer genetic alterations, and immune signatures. Our data provide evidence for a diagnostic marker of LCK and the possible use of LCK as a target for the treatment of tumors.

Up to 50% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) infection, and the surface protein of HBV is essential for the progression of HBV-related HCC. The expression of large HBV surface antigen (LHB) is presented in HBV-associated HCC tissues and is significantly associated with the development of HCC. Gene set enrichment analysis revealed that LHB overexpression regulates the cell cycle process. Excess LHB in HCC cells induced chronic endoplasmic reticulum (ER) stress and was significantly correlated with tumor growth in vivo. Cell cycle analysis showed that cell cycle progression from G1 to S phase was greatly enhanced in vitro. We identified intensive crosstalk between ER stress and cell cycle progression in HCC. As an important regulator of the G1/S checkpoint, p27 was transcriptionally upregulated by transcription factors ATF4 and XBP1s, downstream of the unfolded protein response pathway. Moreover, LHB-induced ER stress promoted internal ribosome-entry-site-mediated selective translation of p27, and E3 ubiquitin ligase HRD1-mediated p27 ubiquitination and degradation. Ultimately, the decrease in p27 protein levels reduced G1/S arrest and promoted the progress of HCC by regulating the cell cycle.

Bronchogenic cysts originate from abnormal foregut budding during embryogenesis. Two pathogenic mechanisms exist: (1) ectopic migration of tracheobronchial precursors forming cysts in extrapulmonary sites, and (2) retained bronchial buds developing pulmonary cysts through mucus accumulation. Despite anatomical variations, all cysts retain respiratory epithelium with mucinous glands, pathognomonically reflecting their embryological origin. Herein, we report an unusual case of bronchogenic cyst in the posterior wall of the gastric fundus with elevated CEA and CA199 in cystic fluid. CT showed that a kind of circular soft tissue density shadow was visible under the submucosa of the stomach floor, with a size of about 3.9 × 3.7 cm, uniform density, and clear boundary. Pathology after surgical resection of the gastric tumor: the cystic wall‐like tissue was locally lined with ciliated columnar epithelium, the mucosa showed chronic inflammation, and foreign body giant cell reaction, calcification, and ossification were observed in the submucosa. The patient was diagnosed as having a bronchogenic cyst in the posterior wall of the gastric fundus and was followed up for 12 months after the operation, with no obvious discomfort.