Na Luo

Esophageal squamous cell carcinoma (ESCC) is recognized as one of the most prevalent malignancies globally, with a notably high incidence in China. The disease often presents with subtle symptoms in its early stages, resulting in diagnoses at mid to late stages, which diminishes the possibility for radical surgical intervention. Additionally, the effectiveness, side effects, and resistance associated with radiotherapy and chemotherapy further constrain their use in treating ESCC. The advent of immune checkpoint inhibitors has expanded the array of immunotherapeutic strategies available for managing this condition. This study aims to delineate the occurrence and distribution of specific immune cell types throughout the progression of ESCC, utilizing a 4‐NQO‐induced murine model that most accurately reflects the initiation and progression of ESCC as observed in humans. This model encompasses various stages of ESCC development, including normal (NOR), inflammation (INF), hyperplasia (HYP), dysplasia (DYS), carcinoma in situ (CIS), and invasive cancer (ICA). Immunohistochemical analysis reveals an increase in the number of Ki67 ⁺ cells correlating with the advancement of ESCC, indicating elevated tumor cell proliferation. Notably, CD4 ⁺ and CD8 ⁺ T cells are prominently observed during the dysplastic stage, while CD20 ⁺ B cells and CD68 ⁺ macrophages are more prevalent during the hyperplastic stage. Furthermore, CD4 ⁺ and CD8 ⁺ T cells are actively involved in tumor recognition and elimination within the esophageal epithelium, whereas CD20 ⁺ B cells and CD68 ⁺ macrophages are primarily localized in the submucosal layer. This study underscores the role of immune cells in the pathogenesis of ESCC and suggests the timely application of immune checkpoint inhibitors may enhance anti‐tumor immunity.

Clear cell renal cell carcinoma (ccRCC) represents the predominant histological subtype of renal cell carcinoma (RCC), constituting approximately 85% of all RCC cases. Recent advancements in therapies aimed at targeting angiogenesis have marked a significant breakthrough in the treatment of ccRCC, with several of these therapies receiving approval for clinical use. Furthermore, the introduction of immune checkpoint inhibitors (ICIs) has demonstrated efficacy in the management of ccRCC. Nonetheless, there is an urgent need for the identification of predictive and prognostic biomarkers, which are currently under investigation. This review offers an extensive examination of the pathological, genomic, and molecular characteristics of ccRCC, with particular emphasis on its immune attributes. Additionally, it addresses the clinical implications of targeted therapies and immunotherapies, whether administered as monotherapy or in combination with traditional or novel agents, while also evaluating the results of pertinent clinical trials. By encompassing a wide range of topics related to ccRCC, from foundational knowledge to clinical applications, this review aims to deepen the understanding of the essential features of ccRCC and to establish a theoretical basis for the formulation of clinical strategies.

Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer that portends a poor prognosis and limited treatment. PTPN2 is a member of the non-receptor protein tyrosine phosphatase family that regulates biological processes by dephosphorylating various signaling molecules. Endoplasmic reticulum stress (ERS) plays a dual regulatory role by promoting both survival and apoptosis. This study aims to elucidate the role of PTPN2 in mediating the pro-apoptotic effects of ERS induced by Thapsigargin (TG), and its influence on the fate of TNBC cells, utilizing both loss-of-function and gain-of-function methodologies. Our findings indicate that PTPN2 modulates TG-induced ERS via the IRE1-XBP1 and PERK/EIF2α/ATF-4 signaling pathways. Furthermore, PTPN2 mitigates the TG-induced reduction in cell proliferation and the concomitant increase in apoptosis. Specifically, PTPN2 appears to inhibit several facets of TG-induced apoptosis, including: (1) Ca²⁺ elevation in mitochondria, (2) the production of reactive oxygen species (ROS), and (3) Bax/Bcl-2 augmentation which dictates mitochondria-mediated apoptosis. Additionally, we observed that the knockdown of PTPN2 enhances TG-induced autophagy; however, our results suggest that autophagy may serve a protective role against TG-induced apoptosis. Consequently, targeting PTPN2 in conjunction with ERS-inducing agents may represent a promising therapeutic strategy for the treatment of TNBC.

Ferroptosis, a novel form of cell death discovered in recent years, is typically accompanied by significant iron accumulation and lipid peroxidation during the process. This article systematically elucidates how tumor metabolic reprogramming affects the ferroptosis process in tumor cells. The paper outlines the basic concepts and physiological significance of tumor metabolic reprogramming and ferroptosis, and delves into the specific regulatory mechanisms of glucose metabolism, protein metabolism, and lipid metabolism on ferroptosis. We also explore how complex metabolic changes in the tumor microenvironment further influence the response of tumor cells to ferroptosis. Glucose metabolism modulates ferroptosis sensitivity by influencing intracellular energetic status and redox balance; protein metabolism, involving amino acid metabolism and protein synthesis, plays a crucial role in the initiation and progression of ferroptosis; and the relationship between lipid metabolism and ferroptosis primarily manifests in the generation and elimination of lipid peroxides. This review aims to provide a new perspective on how tumor cells regulate ferroptosis through metabolic reprogramming, with the ultimate goal of offering a theoretical basis for developing novel therapeutic strategies targeting tumor metabolism and ferroptosis.

[This corrects the article DOI: 10.7150/jca.66773.].

Immunotherapy has revolutionized cancer treatment, especially the emergence of immune checkpoint inhibitors (ICIs), which has been considered as a significant breakthrough in cancer therapy

Editorial: Volume II: Tumor microenvironment in cancer hallmarks and therapeutics

Editorial: Tumor microenvironment in cancer hallmarks and therapeutics