Immune checkpoint inhibitors (ICIs) represent a groundbreaking advance in the treatment of malignancies such as melanoma and non-small cell lung cancer, showcasing substantial therapeutic benefits. Nonetheless, the efficacy of ICIs is limited to a small subset of patients, primarily benefiting those with “hot” tumors characterized by significant immune infiltration. The challenge of converting “cold” tumors, which exhibit minimal immune activity, into “hot” tumors to enhance their responsiveness to ICIs is a critical and complex area of current research. Central to this endeavor is the activation of the cGAS-STING pathway, a pivotal nexus between innate and adaptive immunity. This pathway’s activation promotes the production of type I interferon (IFN) and the recruitment of CD8⁺ T cells, thereby transforming the tumor microenvironment (TME) from “cold” to “hot”. This review comprehensively explores the cGAS-STING pathway’s role in reconditioning the TME, detailing the underlying mechanisms of innate and adaptive immunity and highlighting the contributions of various immune cells to tumor immunity. Furthermore, we delve into the latest clinical research on STING agonists and their potential in combination therapies, targeting this pathway. The discussion concludes with an examination of the challenges facing the advancement of promising STING agonists in clinical trials and the pressing issues within the cGAS-STING signaling pathway research.

Background: Breast cancer-related lymphedema (BCRL) frequently occurs after axillary lymph node dissection and remains incurable even with lymphaticovenular anastomosis. Exercise interventions have emerged as a potential non-pharmacological management approach. However, standardized exercise recommendations tailored to BCRL patients are lacking.Purpose: This study evaluated the impact of high and low compliance exercise interventions, aligned with ACSM recommendations, on quality of life (QOL), shoulder range of motion (ROM), and arm volume in BCRL patients. It further aimed to determine the optimal exercise dosage, assessed via the FITT (frequency, intensity, time, type) principle, that maximizes health benefits for BCRL patients.Methods: Adhering to the PRISMA guidelines for systematic reviews and meta-analyses, we conducted a comprehensive literature search in various databases, including PubMed, Embase, Cochrane Library, and Web of Science, encompassing the period from the inception of these databases to December 2023. We extracted data on exercise form, frequency, intensity, duration, repetitions, and sets from the identified studies. Subsequently, a meta-analysis and review were conducted. The exercise interventions were evaluated based on ACSM recommendations and categorized as either high or low compliance with ACSM standards. Fixed or random effects models were employed to compare outcomes across study subgroups with comparable results. Additionally, funnel plot analyses, sensitivity analyses, and Egger’s and Begg’s tests were conducted to evaluate the potential for bias.Results: 15 studies encompassing 863 patients with BCRL were analyzed. Eleven studies exhibited high ACSM compliance, while four demonstrated low ACSM compliance. Regarding QOL, the overall standard mean difference (SMD) was 0.13 (95% CI: −1.07, 1.33). Specifically, the SMD for the high-adherence subgroup was 0.91 (95% CI: 0.33, 1.49; p = 0.002). For ROM, the overall SMD was 1.21 (95% CI: −0.19, 2.61). For arm volume, the overall SMD was −0.06 (95% CI: −0.22, 0.10). QOL results differed significantly in the high-adherence subgroup, whereas no significant effect on ROM or arm volume was observed.Conclusion: The study revealed significant QOL improvements in patients with high ACSM compliance, contrasted with those with low compliance. Conversely, no notable changes in ROM or arm volume were observed. Notably, the high adherence group tended to show better ROM during exercise and stable arm volume. Future research is needed to validate these findings.

Immune checkpoint blockade-based immunotherapy has become standard of care for multiple cancer types. However, the overall response rates among various cancer types still remain unsatisfactory. There is a pressing clinical need to identify combination therapies to improve efficacy of anticancer immunotherapy. We previously showed that pharmacologic inhibition of PPARγ by GW9662 boosts αPD-L1 and αPD-1 antibody efficacy in treating murine mammary tumors. In addition, we defined sexually dimorphic αPD-L1 efficacy in B16 melanoma. Here, we show a sexually dimorphic response to the combination of GW9662 and αPD-L1 immunotherapy in B16 melanoma. Combination effects were observed in female, but not male hosts. Neither female oöphorectomy impairs, nor does male castration rescue the combination effects, suggesting a sex hormone-independent response to this combination therapy. In diet-induced obese females, melanoma growth remained responsive to the combination treatment, albeit less robustly than lean females. These findings are informative for future design and application of immunotherapy-related combination therapy for treating human melanoma patients by taking gender and obesity status into consideration.

Intraoperative radiotherapy (IORT) is a precise, single high‑dose irradiation directly targeting the tumor bed during surgery. In comparison with traditional external beam RT, it minimizes damage to other normal tissues, ensures an adequate dose to the tumor bed and results in improved cosmetic outcomes and quality of life. Furthermore, IORT offers a shorter treatment duration, lower economic costs and therapeutic efficacy comparable with traditional RT. However, its relatively higher local recurrence rate limits its further clinical applications. Identifying effective radiosensitizing drugs and rational RT protocols will improve its advantages. Furthermore, IORT may not only damage DNA to directly kill breast tumor cells but also alter the tumor microenvironment (TME) to exert a sustained antitumor effect. Specific doses of IORT may exert anti‑angiogenic effects, and consequently antitumor effects, by impacting post‑radiation peripheral blood levels of vascular endothelial growth factor and delta‑like 4. IORT may also modify the postoperative wound fluid composition to continuously inhibit tumor growth, e.g. by reducing components such as microRNA (miR)‑21, miR‑221, miR‑115, oncostatin M, TNF‑β, IL‑6 and IL‑8, and by elevating levels of components such as miR‑223, to inhibit the ability of postoperative wound fluid to induce proliferation, invasion and migration of residual cancer cells. IORT can also modify cancer cell glucose metabolism to inhibit the proliferation of residual tumor cells. In addition, IORT can induce a bystander effect, eliminating the postoperative wound fluid‑induced epithelial‑mesenchymal transition and tumor stem cell phenotype. Insights gained at the molecular level may provide new directions for identifying novel therapeutic targets and approaches. A more comprehensive understanding of the effects of IORT on the breast cancer (BC) TME may further its clinical application. Hence, the present article reviews the primary effects of IORT on BC and its impact on the TME, aiming to offer fresh research perspectives for relevant professionals.

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Breast cancer is the most common female malignancy, but the mechanisms regulating gene expression leading to its development are complex. In recent years, as epigenetic research has intensified, RNA-binding proteins (RBPs) have been identified as a class of posttranscriptional regulators that can participate in regulating gene expression through the regulation of RNA stabilization and degradation, intracellular localization, alternative splicing and alternative polyadenylation, and translational control. RBPs play an important role in the development of normal mammary glands and breast cancer. Functional inactivation or abnormal expression of RBPs may be closely associated with breast cancer development. In this review, we focus on the function and regulatory mechanisms of RBPs in breast cancer, as well as the advantages and challenges of RBPs as potential diagnostic and therapeutic targets in breast cancer, and discuss the potential of RBPs in clinical treatment.