Background: Although immunosenescence-induced difference on overall immune function and immune cell subsets between younger and older populations has been well characterized, the potential effect of patients' age on the efficacy of immune checkpoint inhibitors (ICIs) remains little known. We performed a meta-analysis to investigate whether age differences play a role in cancer immunotherapy efficacy based on a large amount of clinical data.Methods: We conducted a systematic search of PubMed, Embase and MEDLINE for relevant randomized controlled trials. The primary outcome was overall survival (OS) and progression-free survival (PFS) was secondary outcome. The interaction test was used to assess the heterogeneity of HR between younger and older groups.Results: In total, 19 clinical randomized trials involving 11157 patients were included. The pooled HR for OS was 0.73 (95%CI 0.69-0.78) and 0.63 (95%CI 0.52-0.73) for PFS in younger patients receiving ICIs treatments, when compared with younger patients treated with controls. For older patients treated with ICIs, the pooled HR for OS compared with controls was 0.64 (95%CI 0.59-0.69) and 0.66 (95% CI 0.58-0.74) for PFS. The difference on OS efficacy between younger and older patients treated with ICIs was significant (P-heterogeneity=0.025).Conclusions: Immune checkpoint inhibitors significantly improved OS and PFS in both younger and older patients compared with controls, but the magnitude of benefit was clinically age-dependent. Patients 65y can benefit more from immunotherapy than younger patients. Future research should take age difference into consideration in trials and focus on tolerance and toxicity of ICIs in older patients.

Previous studies have shown that lysine-specific demethylase 1 (LSD1) could regulate cell cycle progression through demethylation. The 3′domain of HOX transcript antisense RNA (Hotair) combined with the LSD1/CoREST/REST complex helps LSD1 target the corresponding gene. However, its role in mice's myocardial regeneration is still unclear. The heart from neonatal mice shows strong myocardial regeneration ability, but this ability disappears 7 days after birth. Our study shows that the myocardial tissue highly expresses Hotair and Lsd1 within 1 week after birth, consistent with the myocardial regeneration time window. Knockdown Lsd1 or Hotair expression by RNA interference could inhibit myocardial regeneration and cardiomyocyte proliferation. Our results suggest that Hotair-mediated demethylation of LSD1 may play an important role in myocardial regeneration in neonatal mice.

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset GSE53757 was downloaded from the Gene Expression Omnibus database. The GSE53757 dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein–protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.

4033 Background: Both anti-PD-1 antibodies and molecular antiangiogenic agents have shown promising anti-tumor activities in patients with advanced esophageal cancer. We conducted this single-center phase 2 study to evaluate the efficacy and safety of camrelizumab (anti-PD-1 antibody) plus apatinib (VEGFR2-TKI) in combination with liposomal paclitaxel and nedaplatin in the first-line treatment of patients with esophageal squamous cell carcinoma (ESCC). Methods: Patients with unresectable locally advanced or metastatic ESCC received camrelizumab 200mg d1, liposomal paclitaxel 150mg/m² d1, nedaplatin 50mg/m² d1 and apatinib 250mg d1-14. Treatments were repeated every 14 days for up to 6-9 cycles, followed by maintenance therapy with camrelizumab, apatinib, or both. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. PD-L1 positivity, defined as a combined positive score (CPS) ≥1, was evaluated by immunohistochemistry (IHC). Results: Between Aug 6^th 2018 and Feb 6^th 2019, a total of 29 patients were enrolled. The median age was 62 years (43-70). Most patients were male (22/29, 75.9%) with metastatic disease (25/29, 86.2%). Response evaluation by independent central review was available in 26 patients, with 19 achieving a best response of PR, 6 with SD, and 1 with PD. The ORR and DCR were 73.1% (19/26) and 96.2% (25/26), respectively. Data for PFS and OS were not matured. The most common grade 3/4 adverse events were leucopenia (21/29, 72.4%) and neutropenia (15/29, 51.7%). Two cases of treatment-related SAEs occurred, both led to hospitalization: one patient developed grade 3 febrile neutropenia, grade 4 leucopenia and grade 3 anorexia; another patient developed grade 4 toxic epidermal necrolysis. Conclusions: Camrelizumab plus apatinib in combination with liposomal paclitaxel and nedaplatin could be a new treatment option for patients with unresectable locally advanced or metastatic ESCC. Clinical trial information: NCT03603756.