Exploring a 7-gene prognostic model based on ferroptosis for efficiently guiding immunotherapy in melanoma patients

PurposeAlthough skin cutaneous melanoma (SKCM) is a relatively immunotherapy-sensitive tumor type, there is still a certain fraction that benefits less from treatment. Ferroptosis has been demonstrated to modulate tumor progression in many cancer types. This study focused on ferroptosis-related genes to construct a prognostic model for SKCM patients.Materials and methodsGene expression profiles of SKCM samples were obtained from public databases. Unsupervised consensus clustering was used to determine molecular subtypes related to ferroptosis. Least absolute shrinkage and selection operator (LASSO) and stepwise Akaike information criterion (stepAIC) were applied to construct a prognostic model based on differentially expressed genes between two molecular subtypes.ResultsC1 and C2 subtypes were identified with differential prognosis and immune infiltration. A 7-gene prognostic model was constructed to classify samples into high-FPRS and low-FPRS groups. Low-FPRS group with favorable prognosis had higher immune infiltration and more enriched immune-related pathways than the high-FPRS group. The two groups showed distinct sensitivity to immunotherapy, with the low-FPRS group predicted to have more positive response to immunotherapy than the high-FPRS group. A nomogram based on the FPRS score and clinical features was built for more convenient use.ConclusionsThe critical role of ferroptosis involved in SKCM development was further validated in this study. The prognostic model was efficient and stable to be applied in clinical conditions to support clinicians in determining personalized therapy for SKCM patients especially those with metastasis.     

The neglected brothers come of age: B cells and cancer

The opposing roles of innate and adaptive immune cells in suppressing or supporting cancer initiation, progression, metastasis and response to therapy has been long debated. The mechanisms by which different monocyte and T cell subtypes affect and modulate cancer have been extensively studied. However, the role of B cells and their subtypes have remained elusive, perhaps partially due to their heterogeneity and range of actions. B cells can produce a variety of cytokines and present tumor-derived antigens to T cells in combination with co-stimulatory or inhibitory ligands based on their phenotype. Unlike most T cells, B cells can be activated by innate immune stimuli, such as endotoxin. Furthermore, the isotype and specificity of the antibodies produced by plasma cells regulate distinct immune responses, including opsonization, antibody-mediated cellular cytotoxicity (ADCC) and complement activation. B cells are shaped by the tumor environment (TME), with the capability to regulate the TME in return. In this review, we will describe the mechanisms of B cell action, including cytokine production, antigen presentation, ADCC, opsonization, complement activation and how they affect tumor development and response to immunotherapy. We will also discuss how B cell fate within the TME is affected by tumor stroma, microbiome and metabolism.     

Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion

Background

Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.

Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report

Background:Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART).Methods:From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People''s Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10⁸ cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group.Results:From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P = 0.006) and CD8 level (β = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course.Conclusions:This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted.Registration info:www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).     

免疫治疗在卵巢癌中的应用研究进展

卵巢癌的临床早期症状不明显，筛查手段有限，就诊时常处于晚期阶段，5年生存率仅30%~45%，严重威胁着女性健康。免疫治疗尤其是免疫检查点抑制剂治疗因其持久的抗肿瘤效应已被批准用于晚期或复发性的多种类型癌症的治疗。目前免疫治疗的一些研究进展为卵巢癌患者的临床管理提供了新的机遇与挑战。     

原发纵隔大B细胞淋巴瘤的研究进展

原发纵隔大B细胞淋巴瘤（PMBCL）是一种原发于纵隔的侵袭性大B细胞淋巴瘤，由于其独特的临床和组织学特征，世界卫生组织淋巴肿瘤分类将PMBCL重新分类为一个单独的实体。PMBCL的诊断主要依赖于病理学特征、影像学检查和临床特征等。当前针对PMBCL的治疗方案有很多种，最常用的是R-CHOP和R-EPOCH方案等。放疗对部分患者有益，但也可以导致远期毒性。新药的研发也在不断进行，包括嵌合抗原受体T细胞疗法、抗程序性死亡受体1药物等，治疗后疗效判断和指导下一步的治疗策略主要依赖PET-CT。