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Immunotherapy is currently the most promising clinical treatment for lung cancer, not only revolutionizing second-line therapy but now also approved for first-line treatment. However, its clinical efficiency is not high and not all patients benefit from it. Thus, finding the best combination strategy to expand anti-PD-1/PD-L1-based immunotherapy is now a hot research topic. The conventional use of chemotherapeutic drugs and targeted drugs inevitably leads to resistance, toxic side effects and other problems. Recent research, however, suggests that by adjusting the dosage of drugs and blocking the activation of mutational mechanisms that depend on acquired resistance, it is possible to reduce toxic side effects, activate immune cells, and reshape the immune microenvironment of lung cancer. Here, we discuss the effects of different chemotherapeutic drugs and targeted drugs on the immune microenvironment. We explore the effects of adjusting the dosing sequence and timing, and the mechanisms of such responses, and show how the effectiveness and reliability of combined immunotherapy provide improved treatment outcomes.

BackgroundAccumulating evidence indicates that the B cells play important roles in anti-tumor immunity and shaping tumor development. This study aimed to explore the expression profiles of B cell marker genes and construct a B cell-related gene pairs (BRGPs) signature associated with the prognosis and immunotherapeutic efficiency in non-small cell lung cancer (NSCLC) patients.MethodsB cell-related marker genes in NSCLC were identified using single-cell RNA sequencing data. TCGA and GEO datasets were utilized to identify the prognostic BRGPs based on a novel algorithm of cyclically single pairing along with a 0-or-1 matrix. BRGPs signature was then constructed using Lasso-Cox regression model. Its prognostic value, associated immunogenomic features, putative molecular mechanism and predictive ability to immunotherapy were investigated in NSCLC patients.ResultsThe BRGPs signature was composed of 23 BRGPs including 28 distinct B cell-related genes. This predictive signature demonstrated remarkable power in distinguishing good or poor prognosis and can serve as an independent prognostic factor for NSCLC patients in both training and validation cohorts. Furthermore, BRGPs signature was significantly associated with immune scores, tumor purity, clinicopathological characteristics and various tumor-infiltrating immune cells. Besides, we demonstrated that the tumor mutational burden scores and TIDE scores were positively correlated with the risk score of the model implying immune checkpoint blockade therapy may be more effective in NSCLC patients with high-risk scores.ConclusionsThis novel BRGPs signature can be used to assess the prognosis of NSCLC patients and may be useful in guiding immune checkpoint inhibitor treatment in our clinical practice.

IntroductionRecent developments in immune checkpoint inhibitors (ICIs) have improved the treatment outcomes of esophageal cancer (EC); however, it may initiate immune-related adverse events (irAEs) in some patients. The ICIs’ therapeutic efficacy is associated with irAEs in patients with non-small cell lung cancer or renal cell carcinoma, although this association is unknown in EC. The purpose of this study was to explore the association between irAEs and the efficacy of programmed death 1 (PD-1) inhibitors in EC patients.Patients and methodsThis study included patients with advanced EC treated with PD-1 inhibitors. The patients were divided into two groups according to the occurrence of irAEs. Afterward, the efficacy was compared between the irAE-negative and irAE-positive groups, and we analyzed the predictive factors of irAEs and survival.ResultsOverall, 295 patients were included in this study. Baseline characteristics were balanced in the irAE-negative and irAE-positive groups. In total, 143 (48.47%) patients experienced irAEs. The most frequent irAEs were anemia (49, 16.61%), hyperthyroidism (45, 15.25%), and pneumonitis (44, 14.92%). In total, 33 (11.19%) patients had grade ≥ 3 irAEs and pneumonitis have 15 (5.08%). No grade 5 adverse events were observed. A total of 52 (17.63%) and 91 (30.85%) patients had single and multiple irAEs, respectively. Compared with patients without irAEs, those with irAEs had significantly higher objective response rate (ORR) (37.76% vs. 25.00%, p = 0.018) and disease control rate (DCR) (92.31% vs. 83.55%, p = 0.022). Univariate Cox analyses indicated the significant association between irAEs and improved median progression-free survival (PFS) (10.27 vs. 6.2 months, p < 0.001) and overall survival (OS) (15.4 vs. 9.2 months, p < 0.001). In multivariate analyses, irAEs were independently associated with longer PFS (p = 0.011) and OS (p = 0.002). Moreover, multivariate analysis revealed that cycles > 8, radiation, as well as antiangiogenic therapy were strongly associated with irAEs development (p < 0.001, p = 0.002, and p = 0.025, respectively).ConclusionIn advanced EC, patients with irAEs showed markedly better efficacy in ORR, DCR, PFS, and OS compared with patients without irAEs.

Patients with recurrent pregnancy loss (RPL) account for approximately 1%-5% of women aiming to achieve childbirth. Although studies have shown that RPL is associated with failure of endometrial decidualization, placental dysfunction, and immune microenvironment disorder at the maternal-fetal interface, the exact pathogenesis remains unknown. With the development of high-throughput technology, more studies have focused on the genomics, transcriptomics, proteomics and metabolomics of RPL, and new gene mutations and new biomarkers of RPL have been discovered, providing an opportunity to explore the pathogenesis of RPL from different biological processes. Bioinformatics analyses of these differentially expressed genes, proteins and metabolites also reflect the biological pathways involved in RPL, laying a foundation for further research. In this review, we summarize the findings of omics studies investigating decidual tissue, villous tissue and blood from patients with RPL and identify some possible limitations of current studies.

Irritable bowel syndrome with diarrhea and functional diarrhea are both functional bowel disorders that cause chronic diarrhea. Chronic diarrhea is closely related to daily life and the psychological condition of diarrhea in patients, and probiotics can play a significant role in alleviating chronic diarrhea in some research. Lactobaccilus plantarum CCFM1143 can relieve diarrhea in mice caused by enterotoxigenic Escherichia coli (ETEC); however, its clinical effects remain unclear. This study aimed to assess the effects of CCFM1143 as a therapy for chronic diarrhea patients. Fifty-five patients with chronic diarrhea were randomly assigned into the probiotic group (n = 28) and the placebo group (n = 27), receiving the routine regimen with or without probiotics for 4 weeks, respectively. CCFM1143 can mitigate the apparent clinical symptoms and improve the health status and quality of life of patients. In addition, it could inhibit the increase in interleukin 6 (IL-6) and the decrease in motilin; modulate the short-chain fatty acids, especially acetic and propionic acids; and regulate the gut microbiota, particularly reducing the abundance of Bacteroides and Eggerthella and enriching the abundance of Akkermansia, Anaerostipes, and Terrisporobacter. In addition, treatment with probiotics showed clinical effectiveness in managing chronic diarrhea when compared with the placebo group. The findings could help to develop and further the application of probiotics for chronic diarrhea.

Women with endometriosis may have a defective immune system. However, evidence of the immune responses of endometriosis patients with a history of endometriosis surgery is lacking, and the association between the location of endometriosis lesions and immune responses is unclear. This retrospective study included 117 females with reproductive failure and a history of endometriosis and 200 females with reproductive failure but without endometriosis to analyze their endometrial and peripheral immune responses. The results show that endometriosis was associated with decreased peripheral natural killer (NK) cytotoxicity and increased uterine macrophages. Peripheral NK cytotoxicity at effector-to-target ratios of 25:1 and 50:1 was significantly reduced in women with a history of endometriosis from that of the control group (26.6% versus 33.3% and 36.1% versus 43.3%, respectively, both P < 0.001). Furthermore, after further division of patients into three subgroups according to the location of endometriosis lesions, we observed that NK cytotoxicity in the endometriosis subgroups, especially the mixed endometriosis group, was strongly decreased from that of the controls (P = 0.001). The endometrial CD68+ macrophage proportion in the mixed endometriosis subgroup was higher than that in the control group (2.8% versus 2.1%, P = 0.043). In addition, the baseline estradiol (E2) level was weakly correlated with the percentage of endometrial macrophages (r = 0.251, P = 0.009), indicating a potential association among the endocrine system, endometrial immune environment, and endometriosis. This study indicated that peripheral NK cytotoxicity and endometrial immune cell profiles could be useful for diagnosing and treating endometriosis and endometriosis-related reproductive diseases.

BackgroundThe combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment.MethodsAn electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software.ResultsEleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed.ConclusionMost AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.

Introduction: Recent developments in immune checkpoint inhibitors (ICIs) have improved the treatment outcomes of esophageal cancer (EC); however, it may initiate immune-related adverse events (irAEs) in some patients. The ICIs’ therapeutic efficacy is associated with irAEs in patients with non-small cell lung cancer or renal cell carcinoma, although this association is unknown in EC. The purpose of this study was to explore the association between irAEs and the efficacy of programmed death 1 (PD-1) inhibitors in EC patients. Patients and methods: This study included patients with advanced EC treated with PD-1 inhibitors. The patients were divided into two groups according to the occurrence of irAEs. Afterward, the efficacy was compared between the irAE-negative and irAE-positive groups, and we analyzed the predictive factors of irAEs and survival. Results: Overall, 295 patients were included in this study. Baseline characteristics were balanced in the irAE-negative and irAE-positive groups. In total, 143 (48.47%) patients experienced irAEs. The most frequent irAEs were anemia (49, 16.61%), hyperthyroidism (45, 15.25%), and pneumonitis (44, 14.92%). In total, 33 (11.19%) patients had grade ≥ 3 irAEs and pneumonitis have 15 (5.08%). No grade 5 adverse events were observed. A total of 52 (17.63%) and 91 (30.85%) patients had single and multiple irAEs, respectively. Compared with patients without irAEs, those with irAEs had significantly higher objective response rate (ORR) (37.76% vs. 25.00%, p = 0.018) and disease control rate (DCR) (92.31% vs. 83.55%, p = 0.022). Univariate Cox analyses indicated the significant association between irAEs and improved median progression-free survival (PFS) (10.27 vs. 6.2 months, p < 0.001) and overall survival (OS) (15.4 vs. 9.2 months, p < 0.001). In multivariate analyses, irAEs were independently associated with longer PFS (p = 0.011) and OS (p = 0.002). Moreover, multivariate analysis revealed that cycles > 8, radiation, as well as antiangiogenic therapy were strongly associated with irAEs development (p < 0.001, p = 0.002, and p = 0.025, respectively). Conclusion: In advanced EC, patients with irAEs showed markedly better efficacy in ORR, DCR, PFS, and OS compared with patients without irAEs. [ABSTRACT FROM AUTHOR]