Drug resistance is the main obstacle to achieving a cure in many cancer patients. Reactive oxygen species (ROS) are master regulators of cancer development that act through complex mechanisms. Remarkably, ROS levels and antioxidant content are typically higher in drug-resistant cancer cells than in non-resistant and normal cells, and have been shown to play a central role in modulating drug resistance. Therefore, determining the underlying functions of ROS in the modulation of drug resistance will contribute to develop therapies that sensitize cancer resistant cells by leveraging ROS modulation. In this review, we summarize the notable literature on the sources and regulation of ROS production and highlight the complex roles of ROS in cancer chemoresistance, encompassing transcription factor-mediated chemoresistance, maintenance of cancer stem cells, and their impact on the tumor microenvironment. We also discuss the potential of ROS-targeted therapies in overcoming tumor therapeutic resistance.

Carbohydrates, one of the most important compounds in living organisms, perform numerous roles, including those associated with the extracellular matrix, energy-related compounds, and information. Of these, polymeric carbohydrates are a class of substance with a long history in drug delivery that have attracted more attention in recent years. Because polymeric carbohydrates have the advantages of nontoxicity, biocompatibility, and biodegradability, they can be used in drug targeting, sustained drug release, immune antigens and adjuvants. In this review, various carbohydrate-based or carbohydrate-modified drug delivery systems and their applications in disease therapy have been surveyed. Specifically, this review focuses on the fundamental understanding of carbohydrate-based drug delivery systems, strategies for application, and the evaluation of biological activity. Future perspectives, including opportunities and challenges in this field, are also discussed.

Targeting tumor-associated macrophages (TAMs) has emerged as a promising approach in cancer therapy. This article provides a comprehensive review of recent advancements in the field of nanomedicines targeting TAMs. According to the crucial role of TAMs in tumor progression, strategies to inhibit macrophage recruitment, suppress TAM survival, and transform TAM phenotypes are discussed as potential therapeutic avenues. To enhance the targeting capacity of nanomedicines, various approaches such as the use of ligands, immunoglobulins, and short peptides are explored. The utilization of live programmed macrophages, macrophage cell membrane-coated nanoparticles and macrophage-derived extracellular vesicles as drug delivery platforms is also highlighted, offering improved biocompatibility and prolonged circulation time. However, challenges remain in achieving precise targeting and controlled drug release. The heterogeneity of TAMs and the variability of surface markers pose hurdles in achieving specific recognition. Furthermore, the safety and clinical applicability of these nanomedicines requires further investigation. In conclusion, nanomedicines targeting TAMs hold great promise in cancer therapy, offering enhanced specificity and reduced side effects. Addressing the existing limitations and expanding our understanding of TAM biology will pave the way for the successful translation of these nano-therapies into clinical practice.

Tumor metastasis is the primary cause of mortality in patients with cancer. Several chemokines are identified as important mediators of tumor growth and/or metastasis. The level of CXCL13 has been reported to be elevated in serum or tumor tissues in patients, which mainly functions to attract B cells and follicular B helper T cells. However, the role of CXCL13 in cancer growth and metastasis is not fully explored. In the current study, we found that CXCL13 is not a strong mediator to directly promote tumor growth; however, the mice deficient in CXCL13 had far fewer pulmonary metastatic foci than did the wild-type mice in experimental pulmonary metastatic models. In addition, Cxcl13^−/− mice also had fewer IL-10–producing B cells (CD45⁺CD19⁺IL-10⁺) in the metastatic tumor immune microenvironment than those of wild-type C57BL/6 mice, resulting in an enhanced antitumor immunity. Notably, CXCL13 deficiency further improved the efficacy of a traditional chemotherapeutic drug (cyclophosphamide), as well as that of anti–programmed death receptor-1 immunotherapy. These results suggested that CXCL13 has an important role in regulating IL-10–producing B cells in tumor metastasis and might be a promising target for improving therapeutic efficiency and stimulating tumor immunity in future cancer therapy. Key Points CXCL13 contributes to tumor metastasis by recruiting regulatory B cells. Recruited regulatory B cells affect both innate and adaptive immunity. Lack of CXCL13 increases the efficacy of chemotherapy and PD-1 blockade.

Background: Preoperative estimation of microvascular invasion is of great significance for the clinical decision making in hepatocellular carcinoma. Neutrophil-lymphocyte ratio (NLR) has been reported to be correlated with the poor prognosis of hepatocellular carcinoma. However, the conclusions are conflicting on whether high preoperative NLR level is associated with the presence of microvascular invasion. Aim: To evaluate the association between preoperative NLR level and the risk of microvascular invasion in hepatocellular carcinoma. Methods: Relevant studies were identified by searching PubMed and Embase through February 2019. Fixed or random models were applied to analyze the data based on the heterogeneity. Subgroup, sensitivity, and publication bias analyses were performed. Review Manager 5.3 and STATA software were used for the meta-analysis. Results: A total of 15 studies were eventually included in this meta-analysis. Pooled data based on retrospective cohort studies showed there are more hepatocellular carcinoma patients with vascular invasion (OR 1.74; 95% Cl 1.42, 2.12; P < 0.001) and microvascular invasion (OR 1.62 95% Cl 1.39, 1.89; P < 0.001) in the high NLR group than in the low NLR group. Of case-control studies, a higher preoperative NLR level was found in the microvascular invasion positive group than in the microvascular invasion negative group (OR 0.62; 95% Cl 0.35, 0.90; P < 0.001). The subgroup, sensitivity, and publication bias analyses did not change the results. Conclusion: A higher preoperative NLR level is positively correlated with the risk of microvascular invasion in hepatocellular carcinoma.