Radiation-induced injury remains a significant challenge in the radiotherapy of cancer patients. Ionizing radiation causes various cellular and molecular damages, leading to both acute and chronic organ dysfunction. Its impact extends beyond interrupting standard treatment protocols and adversely affects the quality of life. Therefore, understanding the mechanisms underlying radiation-induced injury and identifying effective treatment strategies are crucial. In this review, we summarize the recent advances in the molecular and cellular mechanisms of radiation-induced injury across various organs and systems, particularly in the lung, gastrointestinal system, brain, skin, and bone. We highlight the roles of oxidative stress, DNA damage response, mitochondrial dysfunction, and epigenetics in radiation pathology, and summarize the relevant signaling pathways and cellular responses involved in radiation damage. Additionally, we discuss the common symptoms, risk factors, and current diagnostic strategies of radiation-induced injuries. Furthermore, this article provides an in-depth review of effective clinical treatments, elucidates their mechanisms of action, and highlights emerging therapeutic approaches, such as stem cell therapy, nanomedicine, and exosome-based interventions, in clinical practice. Despite significant advances in understanding radiation-induced injury, challenges remain in translating molecular insights into effective therapies. The review concludes with a call for integrated, precision medicine-based approaches to better manage radiation-induced injuries and improve patient outcomes.

Cardiac implantable electronic device (CIED) implantation is a minor surgical procedure, with a low complication incidence. Neoplasm occurrence at the CIED pocket is a rare event, and sporadic cases are reported without a comprehensive evaluation. This hybrid study aims to fill this gap through a three-part approach: a new case report, a scoping review with individual patient data (IPD) analysis, and a clinical survey. In March 2024, a male patient with a history of high-grade urothelial cancer referred to our Department with a mass at the CIED pocket. Incisional biopsy confirmed the diagnosis of high-grade urothelial carcinoma. The patient died after 4 months. Through our scoping review and IPD analysis, we collected 56 patients affected by primary neoplasms [40 (71.4%)] and metastasis [16 (28.6%)] at the CIED pocket. Among the primary neoplasms, adenocarcinoma (12; 30.0%) was most frequent in females, while sarcoma (10; 25.0%) was predominant in males. On the other hand, metastasis types were represented by breast cancer (3; 18.8%) in females, and myeloma (2; 13.3%) and melanoma (2; 13.3%) in males. The clinical survey showed data from 471 patients who underwent CIED implantation. No primary neoplasm or metastasis developed at the CIED pocket, also in subjects with history of cancer. Although rare, both primary and metastatic neoplasms may occur at the site of CIED implantation. Vigilant monitoring of CIED patients is essential, particularly when changes at the pocket site arise. Early biopsy and oncologic assessment should be considered in such cases to enable timely diagnosis and intervention.

Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear matrix-associated protein with a pivotal role in glioblastoma (GBM) progression. However, the mechanisms underpinning aberrant SATB2 expression remain elusive. Here, we identify the ubiquitin specific peptidase 10 (USP10) as a deubiquitinase and the deltex E3 ubiquitin ligase 3 L (DTX3L) as a ubiquitin ligase of SATB2 in glioma stem cells (GSCs). USP10 and DTX3L regulate SATB2 ubiquitination at the K266 residue through mutually exclusive interactions and opposing activities. USP10, enriched in GSCs, is induced by transcription factor YY2. Knockdown of USP10 or overexpression of DTX3L markedly downregulates SATB2, resulting in the inhibition of GSC self-renewal and GBM growth, which can be rescued by the overexpression of SATB2. Importantly, pharmacological inhibition of USP10 by Wu-5 effectively suppresses tumor growth. These findings highlight the antagonistic roles of USP10 and DTX3L in the regulation of GBM malignancy and propose USP10 as a potential therapeutic target.

Renal cell carcinoma (RCC) is sometimes referred to as a "metabolic disease", as nearly all types of RCC are associated with the reprogramming of glucose and lipid metabolism. Y-box binding protein 1 (YBX1) plays a crucial regulatory role in the development and progression of various cancers. In the early stages of our study, we analyzed the YBX1 binding proteins in 786-O cells using IP-MS and found that YBX1 is involved in the glycolysis process of RCC. Subsequent experiments showed that YBX1 is an oncogene that is significantly upregulated in RCC. Functionally, YBX1 promotes glycolysis in RCC, and both in vitro and in vivo experiments demonstrate that YBX1 contributes to the malignant progression of RCC. The correlation between YBX1 and Lactate Dehydrogenase A (LDHA) expression was predicted by bioinformatics and further explored in clinical RCC tissues. Mechanistically, YBX1 interacts with LDHA and co-localizes in the cytoplasm. CUT&Tag and functional experiments further revealed that YBX1 regulates LDHA through transcription. Additionally, YBX1 and LDHA activate the nuclear factor kappa-B (NF-κB) signaling pathway. Silencing the LDHA gene or using an LDHA inhibitor rescued the YBX1-mediated activation of the NF-κB signaling pathway and inhibited lactic acid production and RCC cell proliferation. In conclusion, these findings provide new insights into the oncogenic role of YBX1 in glycolysis and suggest that the YBX1-LDHA-NF-κB axis may represent a promising therapeutic target of RCC.

In recent years, immune checkpoint inhibitor (ICI) therapy has achieved a breakthrough in cancer treatment. By targeting and blocking immune checkpoint molecules on T cells, ICIs release inhibited anti-tumor immune responses, demonstrating durable clinical efficacy and improved long-term survival across multiple cancer types. However, only a minority of cancer patients currently benefit from ICI treatment, with primary resistance observed in most malignancies. Clarifying the mechanisms underlying primary resistance to ICI therapy is conducive to the development of effective combination strategies for overcoming drug resistance. This review systematically examines the molecular basis of primary resistance to ICIs through following aspects: tumor lymphocyte infiltration phenotype, interferon signaling pathways, antigen presentation machinery, and tumor cell-intrinsic oncogenic signaling pathways, which may provide novel therapeutic targets and rational combination strategies for cancer immunotherapy.

Unplanned readmissions of patients with cancer increase healthcare costs and disrupt care. Although well-studied in surgical oncology, data on patients receiving active treatment for advanced cancer remain limited. This study examined the causes, clinical characteristics, and outcomes of unplanned readmissions.

This retrospective, multicenter study included patients with advanced solid tumors from six South Korean university hospitals who had unplanned readmissions within 1 month of prior hospitalization in 2019. Patients with terminal cancer who did not receive active treatment were excluded. Readmissions were categorized as Cancer Progression (e.g., worsening symptoms), treatment-related (e.g., therapy complications), or other (e.g., non-cancer conditions). Additional unplanned hospital use within 1 month post-discharge was analyzed in survivors with 6-month follow-up data.

Among the 542 patients, readmissions were classified as cancer progression (42.6%), treatment-related (37.3%), or other (20.1%). The cancer progression group had the longest hospital stay (median, 12 days) and the highest mortality (23.4%). The Treatment-Related group had shorter stays (8 days) and lower mortality (8.4%). Among the 445 survivors, 24.9% had unplanned hospital visits within 1 month post-discharge. Home discharge increased the likelihood of these events (adjusted odds ratio: 4.82 for readmissions, 2.65 for emergency department visits).

Cancer progression was the leading cause of readmission and was associated with prolonged hospital stays and high mortality rates. Home discharge is a key predictor of early additional unplanned hospital visits, indicating the need for careful post-discharge monitoring in this population.

Oncolytic herpes simplex virus (oHSV) therapy is a live virus-based immunotherapy that lyses tumor cells which release antigens and activate antitumor immunity. oHSV therapy has been shown to increase ATP production and release of extracellular ATP (eATP). In the extracellular tumor microenvironment, eATP functions as an immune-activating damage-associated molecular pattern but is hydrolyzed to extracellular adenosine (eADO), which can be immune-suppressive. eADO is generated by the sequential action of ectoenzymes CD39 and CD73 (NT5E). Here, we examined the role of immunosuppressive eADO signaling in regulating antitumor immune efficacy of oHSV.

We evaluated changes in eADO signaling in vitro and in patient specimens after virotherapy. A genetic CD73 knock-out mouse model and blocking antibodies were used to assess the impact of CD73 on virotherapy in two different solid tumor models. Single-cell RNA sequencing was employed to assess changes in immune cell infiltration and communication. Flow cytometric immunophenotyping and immunofluorescent imaging were utilized to confirm single-cell sequencing predicted changes in tumor microenvironment.

Transcriptomic analysis of patient tumors pre-virotherapy and post-virotherapy with CAN-3110 revealed increased expression of the adenosine receptor gene ADORA2B after treatment. High NT5E gene expression, as well as gene signatures suggestive of adenosine signaling, correlated with a significantly worse prognosis for patients with solid tumors. Single-cell sequencing of immune cells recruited to tumor-bearing brain hemispheres in CD73 knockout mice revealed an increase in macrophage-mediated antigen presentation and CD4⁺ T cell cross-communication. Intracranial tumor-bearing CD73 knock-out mice treated with oHSV showed significant therapeutic improvement as the result of oHSV compared with wild-type mice. Combination of virotherapy with CD73 antibody blockade also resulted in enhanced antitumor efficacy.

Here, we identify that immunosuppressive eADO signaling in the TME is a major barrier to oHSV therapy and CD73 blockade prevents tumor immune escape. The combination of oHSV with CD73 blockade supports the development of an antitumor immune memory response in solid tumors. This study supports clinical development of this combination strategy.

Peptide presentation on human leukocyte antigens (HLAs) is essential for initiating T-cell responses and all consequences of this presentation including anticancer immunity or immune escape. Many studies have relied on in silico prediction tools rather than biological measurement of HLA presentation to study these effects. To better assess the frequency and consequences of neoantigen presentation, we overexpressed 125 combinations of full-length neoantigens and one HLA class I allele to experimentally validate presentation of mutated and non-mutated HLA ligands through HLA ligand isolation followed by tandem mass spectrometry. A successful presentation was observed only in 22% of predicted cases with strong implications on previously described downstream effects. For example, the association of HLA loss of heterozygosity with predicted neoepitopes was challenged for 58% (73/125) of combinations. Furthermore, when testing 51 sequences used for personalized messenger RNA neoepitope vaccines, we observed that clinical responses were independent of the presentation status of the neoepitopes. Even a presumably neoepitope-specific and strongly expanded T cell receptor clone from a neoantigen vaccination study could not be linked to a successfully presented neoepitope. Overall, these data highlight the importance of validating the presentation of neoepitopes to fully understand our interpretation of clinical mutation-specific responses and their related effects, including immune evasion.

Mismatch repair deficiency (dMMR) colorectal cancer (CRC) is characterized by abundant tumor-infiltrating lymphocytes and tertiary lymphoid structures (TLSs). However, while B cells are pivotal for TLS formation, their function and the signaling pathways driving their activation in dMMR CRCs remain undefined.

Data from The Cancer Genome Atlas (TCGA) database analyzed by XCELL method and multiplex immunofluorescence (MIF) staining tissue slides were used to compare the abundance and distribution of TLSs and B cell populations between dMMR and proficient MMR cohorts. Then MLH1 knockdown models both in vitro and in vivo were used to mimic dMMR/high microsatellite instability (MSI-H) tumors and explore the influence of tumor cells on B cell behavior.

TCGA analysis and MIF staining revealed a significant association between memory B cell abundance, TLS formation, and improved prognosis in dMMR CRCs. In vivo MLH1 knockdown models showed that B cell depletion enhanced tumor growth and reduced the efficacy of anti-PD-1 treatment in dMMR CRCs. Furthermore, in vitro experiments demonstrated a dsDNA/STING/type I interferon (IFN)/STAT1/ccl19 signaling pathway mediating the dMMR-induced increase in memory B cells.

In conclusion, these findings show that CCL19 generated by STING/type I IFN/STAT1 pathway in dMMR/MSI-H CRC cells can promote the expansion of memory B cells, which suppresses tumor growth and enhances the efficacy of PD-1 blockade.

Obesity promotes carcinogenesis through interlocking metabolic, inflammatory, immune, and hormonal pathways. We narratively synthesize recent meta-analyses and selected cohort studies that examine adiposity-principally body mass index (BMI) and waist circumference-in relation to cancer incidence. Across the 13 cancers designated by the U.S. National Cancer Institute as obesity-associated, risk elevations are generally consistent, though magnitudes vary by histology (e.g., esophageal adenocarcinoma vs. squamous cell carcinoma), anatomic subsite (gastric cardia vs. non-cardia), sex or menopausal status, and adiposity metric, with central adiposity often revealing additional risk beyond BMI. Evidence is mixed for several sites (e.g., pancreas and thyroid), and emerging but less established signals are noted for oral cavity, melanoma, bladder, non-Hodgkin lymphoma, and leukemia. We also review prevention data: observational studies and select trials suggest that intentional weight loss-via lifestyle interventions, pharmacotherapy (including glucagon-like peptide-1 receptor agonists), or bariatric surgery-can reduce overall or site-specific cancer incidence, although estimates are heterogeneous and causal certainty is limited. Taken together, biologic plausibility and convergent epidemiology support obesity as a modifiable cancer risk factor. Future studies are warranted using standardized exposure definitions, consistent stratification, and rigorous control of confounding to improve comparability. Adequately powered, long-term randomized or quasi-experimental studies may further refine effect sizes and inform precision prevention for obesity-related cancers.