Immune checkpoint blockade (ICB) has emerged as a promising immunotherapeutic approach for the treatment of various tumors. However, the efficacy of this therapy is limited in a subset of patients, and it is important to develop strategies to enhance immune responses. Studies have demonstrated a critical role of gut microbiota in regulating the therapeutic response to ICB. Gut microbiota composition, diversity, and function are mediated by metabolites, such as short-chain fatty acids and secondary bile acids, that interact with host immune cells through specific receptors. In addition, gut bacteria may translocate to the tumor site and stimulate antitumor immune responses. Therefore, maintaining a healthy gut microbiota composition, for instance through avoiding the use of antibiotics or probiotic interventions, can be an effective approach to optimize ICB therapy. This review summarizes the current understanding of the microbiota-immunity interactions in the context of ICB therapy, and discusses potential clinical implications of these findings.

BACKGROUND:The N-6-adenine-specific DNA methyltransferase 1 (N6AMT1) is the only writer responsible for DNA 6mA modifications. At present, its role in cancer is still unclear, and further systematic pan-cancer analysis is needed to explore its value in diagnosis, prognosis and immunological function.METHODS:The subcellular localization of N6AMT1 was explored by UniProt and HPA database. The expression data and prognosis data of N6AMT1 were downloaded from the UCSC (cohort: TCGA pan-cancer), and the diagnostic and prognostic value of N6AMT1 in pan-cancer was explored. The value of N6AMT1-guided immunotherapy was explored through three cohorts (GSE168204, GSE67501 and IMvigor210 cohort). The correlation between N6AMT1 expression and tumor immune microenvironment was explored using CIBERSORT and ESTIMATE calculation methods, combined with TISIDB database. The biological role of N6AMT1 in specific tumors was explored by GSEA method. Finally, we explored chemicals affecting N6AMT1 expression through the CTD.RESULTS:N6AMT1 is mainly localized in the nucleus and differentially expressed in 9 cancer types. In addition, N6AMT1 showed early diagnostic value in 7 cancers and showed potential prognostic value in multiple cancer types. We also demonstrated that N6AMT1 expression was significantly associated with immunomodulator-related molecules, infiltration of lymphocyte subsets, and biomarkers of immunotherapy response. Furthermore, we show that N6AMT1 is differentially expressed in the immunotherapy cohort. Finally, we explored 43 chemicals that can affect N6AMT1 expression.CONCLUSIONS:N6AMT1 has shown excellent diagnostic and prognostic capabilities in a variety of cancers, and it may reshape the tumor microenvironment and contribute to the ability to predict response to immunotherapy.

随着免疫检查点抑制剂在临床的广泛应用,免疫相关不良反应的发生也逐渐受到重视,其中免疫介导的皮肤毒性是常见的不良反应.现代医学常以糖皮质激素治疗免疫介导的毒性反应,但长期大剂量使用糖皮质激素亦会产生一系列问题.中医依据辨证论治的原则,联合糖皮质激素治疗免疫介导的皮肤毒性,具有较好的疗效,本文就免疫相关皮肤毒性的中西医治疗策略进行综述及验案分析.

This study aimed to evaluate the efficacy and safety of “highly exposed Chinese herbal medicine” combined with apatinib as maintenance treatment following first-line or second-line chemotherapy in patients with ES-SCLC. A total of 23 patients with ES-SCLC were included in this single-arm prospective study (ChiCTR2100045255). “Highly exposed Chinese herbal medicine” combined with apatinib was administered each day after the chemotherapy for maintenance treatment. The primary endpoint of the study was median PFS, while the secondary endpoints included median OS, DCR, ORR, AE, and the association of “highly exposed Chinese herbal medicine” with PFS and OS. Three and 16 patients achieved partial response (PR) and stable disease (SD), respectively, and four patients were with disease progression (PD). The ORR of the patients was 13.0%, DCR was 83.0%, median PFS was 5.0 months, and median OS was 18.0 months. The major AE included secondary hypertension and hand-foot syndrome. Oral intake of Chinese herbal medicine for ≥ 6 months was associated with longer PFS. Hand-foot syndrome was an independent predictive factor for PFS. The statistical analysis suggested no independent influencing factors for OS. “Highly exposed Chinese herbal medicine” combined with apatinib is effective and relatively safe as the maintenance treatment for ES-SCLC patients who undergo first-line or second-line chemotherapy.

Gallbladder cancer（GBC）is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developingCurrently,GBC has a low early diagnosis rate and an extremely poor prognosis,leading to major problems for treatment of GBC.Liver invasion and metastasis one of the main causes of its poor prognosis,with its average overall survival of 6 months,

目的 观察加味半夏泻心汤联合亮菌混合液保留灌肠治疗伊立替康(CPT-11)肠黏膜损伤的临床疗效.方法 将2016年10月至2018年5月安徽医科大学第一附属医院及安徽省立医院收治的接受过CPT-11单药或联合方案化疗,并出现急性或迟发性腹泻的病人40例,按照随机数字表法随机分为两组,治疗组(20例)和对照组(20例),治疗组采用加味半夏泻心汤联合亮菌混合液保留灌肠治疗,对照组采用亮菌混合液保留灌肠治疗,2周为一疗程,2周后分别观察两组病人的总有效率、症状和体征、生活质量及不良反应等.结果 治疗组和对照组的总有效率分别为90％和70％,两组比较差异有统计学意义(χ2=9.668,P=0.022);治疗后治疗组的腹痛及大便性状改变均较对照组下降明显,分别P=0.039,P=0.029,治疗组优于对照组;经治疗后,治疗组卡氏评分提升较对照组大(两组卡氏评分均数的方差分析:F=6.066,P=0.018);两组在治疗过程中均未见明显不良反应.结论 加味半夏泻心汤联合亮菌混合液保留灌肠治疗CPT-11肠黏膜损伤疗效优于单纯亮菌混合液灌肠.

目的 探讨益气通络解毒方联合化学疗法治疗晚期结直肠癌的临床疗效.方法 将124例转移性结直肠癌患者随机分为观察组和对照组,每组62例,观察组患者采用益气通络解毒方联合化学治疗,对照组采用单纯化学治疗.结果 观察组患者实体瘤疗效明显优于对照组(P<0.05),观察组患者骨髓抑制及恶心呕吐分级较对照组明显减轻(P<0.05).结论 益气通络解毒方可提高晚期结直肠癌的疗效,减轻化学治疗引起的骨髓抑制和消化道不良反应.

Objective To evaluate the efficacy and safety of irinotecan plus platinum chemotherapy and irinotecan monotherapy for the treatment of recurrent ovarian cancer.Method The databases included Cochrane Database of Systematic Reviews,Cochrane Central Register of Controlled Trials,Medline,EMBASE,National Research Register,Conference Papers Index,Open Grey,CNKI,Wanfang data,etc.Quality assessment and meta-analysis were performed for randomized controlled trials that met the inclusion criteria.Results Six randomized controlled trials involving 438 participants were included.Irinotecan plus platinum was equal to irinotecan in complete response rate (OR =0.53,95 ％ CI;0.25 to 1.09,P =0.08),but better in partial response rate (OR =0.40,95 ％ CI:0.27 to 0.60,P ＜ 0.000 01) and overall response rate (OR =0.34,95％ CI:0.23 to 0.51,P ＜ 0.000 01).In safety,higher incidence rate of WBC (OR =0.25,95 ％ CI:0.10 to 0.65,P =0.005) and PLT (OR =0.34,95 ％ CI:0.16 to 0.71,P =0.004) myelosuppression and tolerable incidence rate of anemia (OR =0.71,95％ CI:0.37 to 1.33,P =0.28),nausea and vomiting (OR =0.25,95％ CI:0.05 to 1.25,P =0.09),diarrhea (OR =0.79,95％ CI:0.44 to 1.43,P =0.44),neurotoxicity (OR =0.86,95％ CI:0.44 to 1.06,P =0.65) and hepatic dysfunction (OR =0.60,95％ CI:0.27 to 1.33,P =0.21) were confirmed for irinotecan plus platinum therapy compared with irinotecan monotherapy.Conclusions For recurrent ovarian cancer patients,after eliminating chemotherapy taboo,using irinotecan plus platinum could bring better efficacy.But for those whose white blood cells (WBC) or platelets (PLT) reduce significantly,associated with bleeding tendency,or inability to use drugs which can improve WBC and PLT levels,irinotecan monotherapy would be considered.