TP53 has been proved to be associated with cytotoxic T-cell induced apoptosis, however, the association between TP53 and the benefit of immunotherapy in melanoma has not been studied. In the present study, we examined the relationship between TP53 mutation and response to CTLA-4 blockade in metastatic melanoma by analyzing the data from one public cohort consisting of 110 patients with metastatic melanoma. The sequencing, mRNA and survival data of 368 patients with skin melanoma from The Cancer Genome Atlas (TCGA) was used to explore the underlying mechanism. TP53 mutation was associated with significant poorer progression-free survival (HR, 2.25; 95% CI, 1.15–4.37; P = 0.014), poorer overall survival (HR, 2.05; 95% CI, 1.02–4.13; P = 0.040) and trend of poorer response (OR, 0.20; 95% CI, 0.02–1.62; P = 0.131). The correlations were significant in multivariate analysis including lactate dehydrogenase, tumor mutational burden and tumor stage (P < 0.05). In TCGA, no association was observed between TP53 mutation and survival (P = 0.55). The mRNA expression of FAS was lower in patients with TP53 mutation than TP53 wild-type. Our findings suggest that TP53 mutation is a potential negative predictor of metastatic melanoma treated with CTLA-4 blockade.

Keloids represent one extreme of aberrant dermal wound healing. One of the important characteristics of keloids is uncontrolled fibroblasts proliferation. However, the mechanism of excessive proliferation of fibroblasts in keloids remains elusive. In this study, we demonstrated that TRAF4 was highly expressed in keloid fibroblasts and promoted fibroproliferation. We investigated the underlying molecular mechanism and found that TRAF4 suppressed the p53 pathway independent of its E3 ubiquitin ligase activity. Specifically, TRAF4 interacted with the deubiquitinase USP10 and blocked the access of p53 to USP10, resulting in p53 destabilization. Knockdown of p53 rescued cell proliferation in TRAF4-knockdown keloid fibroblasts, suggesting that the regulation of proliferation by TRAF4 in keloids relied on p53. Furthermore, in keloid patient samples, TRAF4 expression was inversely correlated with p53ep21 signaling activity. These findings help to elucidate the mechanisms underlying keloid development and indicate that blocking TRAF4 could represent a potential strategy for keloid therapy in the future.

This study was conducted to identify factors associated with lymph node (LN) metastasis in nasopharyngeal carcinoma (NPC) patients, analyze node distribution patterns, and explore the prognostic value of the LN metastasis level for survival. We included 2994 patients with primary NPC diagnosed between 2006 and 2015 with information in the Surveillance, Epidemiology, and End Results (SEER) database. Patients' demographic and clinicopathologic features were compared according to LN status using chi-squared tests. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates were calculated by the Kaplan–Meier method, and the differences were estimated by log-rank tests. Multivariate Cox proportional hazard models were used to evaluate independent risk factors for OS and CSS. Logistic regression was used to evaluate the risk of each LN metastasis category for distant metastasis. There were 695 patients in the N0 stage and 2299 with LN metastasis (classified as stage N1, N2, or N3). The overall incidence of LN metastasis was 76.8%. Sex and T stage were not associated with LN metastasis. Older patients had a significantly worse 5-year OS and CSS than younger patients. In terms of histologic type, keratinizing squamous cell carcinoma had the lowest 5-year OS and CSS at 48.2% and 53.8%, respectively. The most common nodal involvement level was II (65.9%), followed by III (29.1%), V (25.6%), I (17.6%), IV (15.7%), and retropharynx (13.5%). The skip metastasis rate was 5.7% (130/2299). Patients with only level II metastasis (classified as level 2) was the most common category, accounting for 30%. Compared to level 2, patients with only level I (classified as level 1) had an OR of 2.101 (95% CI: 1.090–4.047, P=0.027) for distant metastasis, patients with simultaneous levels II, III, IV, and V (classified as levels 2345) had the highest OR of 4.064 (95% CI: 2.155–7.666, P < 0.001) for distant metastasis, and level 24 had an OR of 3.003 (95% CI: 1.074–8.395, P=0.036) for distant metastasis. In survival analysis, levels 235 had a significant HR of 1.708 (95% CI: 1.089–2.678, P=0.020) for CSS compared to level 2 after adjustment for age, sex, race, histology, TNM (tumor, node, and metastasis) stage, and treatment.

Objective: To evaluate the distant metastatic patterns and prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in de novo metastatic nasopharyngeal carcinoma (mNPC) using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients with de novo mNPC who had been diagnosed between 2004 and 2016 were identified from the SEER database. Kaplan-Meier analysis was used to calculate OS and CSS. Log-rank tests were employed to measure survival variation among subgroups. Individual predictors of CSS and OS were examined using Cox proportional-hazards regression models in patients with de novo mNPC. Results: We evaluated 224 patients with de novo mNPC who matched our inclusion criteria. Three-year CSS and OS for the whole cohort was 29.8% and 27.9%, respectively. Univariate analysis indicated that CSS and OS were influenced by age, histology, radiotherapy, chemotherapy, and liver metastasis. Neither the number of metastatic sites nor their specific location in bone, lungs, distant lymph nodes or brain significantly affected CSS or OS. The aforementioned independent prognosticators continued to significantly influence survival following multivariate analysis. Taking distant metastasis without liver involvement as a reference, liver metastasis was associated significantly with shorter OS at a hazard ratio (HR) of 1.581 (P = .021) and CSS at a HR of 1.643 (P = .016). Older age, keratinizing squamous cell carcinoma, no chemotherapy, and no radiotherapy were also prognosticators for poor OS (P < .05). Similar results were documented for CSS (P < .05). Conclusion: For patients with de novo mNPC, liver metastasis is an independent prognosticator for inferior CSS and OS.

B7-H3 is over-expressed in multiple types of solid tumors, making it an ideal target for chimeric antigen receptor (CAR)-T therapy. Here, we first report a case of multiple basal cell carcinoma (BCC) patient treated with humanized monoclonal anti-B7-H3 CAR-T cells through direct intratumoral injection. After three dose-escalated injections, the lesion in the abdomen decreased by 40% in volume, shrank from bulging to flat, but was not eradicated completely. The large lesion in the forehead became dry from original ulcer and bleeding. The adverse events observed were itching, myalgia, and redness. Immunohistochemistry analysis demonstrated that B7-H3-positive tumor cells and B7-H3 expression intensity were reduced after injections of CAR-T cells. The number of infiltrating CD3 T cells increased significantly but mainly located outside the tumor region. Subsequently, high levels of TGF-β in the tumor area were observed, suggesting that solid tumor microenvironment may hinder the infiltration and effect of CAR-T cells. In summary, in this particular case report, intratumoral injection of B7-H3 CAR-T cells partially controls tumor growth in the BCC patient with minor adverse events. The efficacy and safety of B7-H3 CAR-T therapy need to be further investigated with a larger cohort of patients. Although only one clinical case is reported here, the anti-B7-H3 CAR-T cell therapy should be considered as a treatment option for solid tumors in the future. This clinical trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) with registration number ChiCTR2100044386.