Background. Nowadays, PD-1/PD-L1 inhibitors are widely used to treat various malignant tumors. However, during the immunotherapy in a few patients, a flare-up of tumor growth occurred. This new pattern of progression is called hyperprogressive disease (HPD). Patients and Methods. The retrospective study included 377 patients with various malignant tumors treated with PD-1 inhibitors (nivolumab or pembrolizumab) in the Chinese PLA General Hospital from January 2015 to January 2019. Clinicopathologic variables, tumor growth rate (TGR), and treatment outcomes were analyzed in patients with pan-cancer treated with PD-1 inhibitors. HPD was defined as the difference of TGR before and during immunotherapy exceeding 50%. Results. In 38 of 377 patients (10.08%), HPD occurred after treatment with PD-1 inhibitors. Patients with HPD had lower overall survival (OS) than those without HPD (median OS, 3.6months (95% CI, 3.0–4.2) vs. 7.3 months (95% CI, 5.9–8.7); ). Factors related to HPD include more than 2 metastatic sites, ECOG performance , hepatic metastases, and lactate dehydrogenase level greater than normal upper limit. KRAS status was significantly associated with HPD in patients with colorectal cancer. In the exploratory predictors’ analysis, the rapid increase of characteristic tumor markers (such as CEA in colorectal cancer, CA199 in pancreatic cancer and cholangiocarcinoma) within one month was found to be associated with the occurrence of HPD. Conclusions. HPD was developed with different rates in a variety of malignant tumor patients treated with PD-1 inhibitors and related to some clinicopathological features and poor prognosis. Tumor markers, especially CA199, might be served as early predictors of HPD.

Background. The application of immunotherapy is gradually increasing in advanced bile tract carcinoma (BTC), but only some patients could benefit from it. Validated biomarkers can screen out the beneficiaries. Therefore, the objective of this research is aimed at exploring the predictive value of lung immune prognostic index (LIPI) in advanced BTC patients receiving immunotherapy. Methods. This study was conducted on 110 BTC patients. The cut-off value of the derived neutrophil-to-lymphocyte (dNLR) ratio was obtained by the ROC curves to predict the tumor progression rate at the 6^th month. The high levels of dNLR (≥the cut-off value) and lactate dehydrogenase (≥the upper limit of normal) were considered to be two risk factors for LIPI. Based on these two risk factors, patients were categorized into 3 groups based on risk factors: 0 for the good group, 1 for the intermediate group, and 2 for the poor group. Due to the limited number of patients in the poor group, it was integrated into the intermediate group to be the intermediate/poor group. Finally, the subjects were divided into two groups: LIPI-good and LIPI-intermediate/poor. Results. The results shed light on the 110 BTC patients’ LIPI in advanced BTC patients receiving immunotherapy, indicating that the cut-off value of dNLR was 1.74. According to the risk stratification, 38 (34.5%) patients had a good LIPI score, whereas the LIPI score was intermediate/poor in 72 (65.5%). In addition, patients with good LIPI were related to longer progression-free survival (PFS) and overall survival (OS), compared to those with intermediate/poor LIPI (12.17 months vs. 3.17 months; 20.2 months vs. 8.7 months). According to multivariate analysis, the intermediate/poor LIPI group was independently correlated with over 2.3 times greater risk of tumor progression ( ; 95% CI, 1.395-3.796; ) and over 1.8 times greater risk of death ( ; 95% CI, 1.076-3.275; ) than the good group. Moreover, the result also revealed that there were significant differences of DCR for patients of the good group and the intermediate/poor group (86.8% vs. 65.3%; ). Conclusion. Finally, this study verifies, for the first time, that LIPI is an independent factor affecting the survival and clinical efficacy of advanced BTC patients receiving immunotherapy. It may be difficult for patients with intermediate/poor LIPI to benefit from immunotherapy.

Immunotherapy, led by programmed cell death protein-1 (PD-1) inhibitors, has emerged as a prominent antitumor therapy, yet prognostic challenges persist in pancreatic cancer (PC). This retrospective, single-center study evaluated prognostic factors in advanced PC patients treated with PD-1 inhibitors at the PLA General Hospital's Oncology Department from 2015-2022. With ethics approval by the Ethics Committee of the General Hospital of the People's Liberation Army (S2021-228-03), we analyzed 126 patients using Kaplan-Meier and Cox models. p < .05 was considered a statistically significant difference. Median overall survival (mOS) and progression-free survival (mPFS) were 12.1 and 4.6 months, respectively. Significant mOS predictors were surgery history (44.2 months vs. 10 months, *p = .022), absence of liver metastases (44.2 months vs. 6.4 months, *p = .034), and baseline CA19-9 ≤ 216.15 U/ml (18.5 months vs. 9.2 months, *p = .049). For mPFS, histologic differentiation (5.5 months vs. 3.2 months, *p = .022) and first-line PD-1 inhibitor use (5.1 months vs. 1.5 months, ***p = .001) were key. Subgroup analyses highlighted early progression in low histologic differentiation and earlier death without surgery. History of surgery, absence of liver metastases, baseline CA19-9 level, and histologic intermediate/high differentiation may predict PD-1 inhibitor efficacy in advanced PC, pending validation in prospective trials.

Telomerase, crucial for maintaining telomere integrity and genomic stability, is typically silenced in somatic cells with advancing age. In this study, we identify circHERC1 as a regulator of telomerase reverse transcriptase (TERT) transcription. Specifically, circHERC1 binds to the TERT promoter, facilitating the recruitment of RNA polymerase II and c-Fos, thereby activating TERT expression. Notably, circHERC1 expression exhibits a decline with age, which correlates with reduced telomerase activity. Restoration of circHERC1 expression enhances telomerase activity, promotes telomere elongation, and reverses aging-associated phenotypes. Furthermore, delivery of circHERC1 using adeno-associated virus vectors or extracellular vesicles effectively restores telomerase activity, preserves telomere integrity, and mitigates senescence. This intervention leads to improvements in cognitive function, physical performance, and a reduction in inflammation. These findings highlight the important role of circHERC1 in telomerase regulation and the aging process, positioning it as a potential therapeutic target for antiaging interventions.