Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by early metastasis, rapid tumor growth and poor prognosis. In recent decades, the epidemiology, initiation and mutation characteristics of SCLC, as well as abnormal signaling pathways contributing to its progression, have been widely studied. Despite extensive investigation, fewer drugs have been approved for SCLC. Recent advancements in multi-omics studies have revealed diverse classifications of SCLC that are featured by distinct characteristics and therapeutic vulnerabilities. With the accumulation of SCLC samples, different subtypes of SCLC and specific treatments for these subtypes were further explored. The identification of different molecular subtypes has opened up novel avenues for the treatment of SCLC; however, the inconsistent and uncertain classification of SCLC has hindered the translation from basic research to clinical applications. Therefore, a comprehensives review is essential to conclude these emerging subtypes and related drugs targeting specific therapeutic vulnerabilities within abnormal signaling pathways. In this current review, we summarized the epidemiology, risk factors, mutation characteristics of and classification, related molecular pathways and treatments for SCLC. We hope that this review will facilitate the translation of molecular subtyping of SCLC from theory to clinical application.

Executive functions in children with developmental language disorder: a systematic review and meta-analysis.

Background: The purpose of the current study was to assess the differences between children with developmental language disorder (DLD) and typically developing (TD) children in their performance of executive functions from working memory, inhibitory control, and cognitive flexibility. Methods: We performed a systematical search of PubMed, Embase, Cochrane, and Web of Science for case control studies (published in English between January 1, 1950, and October 11, 2023) comparing the differences in the performance of executive functions between DLD and TD children. Results: Forty eligible studies were included in the present study (N = 3,168 participants). In comparison with TD children, DLD children exhibited significantly poorer performances in all six verbal working memory tasks (backward digit recall task, SMD -1.4321, 95% CI -2.2692 to -0.5950; listening recall task, SMD -1.4469, 95% CI -1.7737 to -1.1202; counting recall task, SMD -0.9192, 95% CI -1.4089 to -0.4295; digit recall task, SMD -1.2321, 95% CI -1.4397 to -1.0244; word list recall task, SMD -1.1375, 95% CI -1.5579 to -0.7171; non-word recall task, SMD -1.5355, 95% CI -1.8122 to -1.2589). However, regarding inhibitory control and cognitive flexibility, the differences between DLD and TD children depended on specific circumstances. In subgroup analyses of all verbal working memory tasks, DLD children presented notably lower performance than TD children in both the monolingual English and monolingual non-English groups, and in both the preschooler and school-aged groups. Conclusion: This study proves that verbal working memory deficits can be seen as a marker for children with DLD and are not affected by age or language type. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=391070, CRD42023391070.

Discovery of novel 4-trifluoromethyl-2-anilinoquinoline derivatives as potential anti-cancer agents targeting SGK1.

Given the critical necessity for the development of more potent anti-cancer drugs, a series of novel compounds incorporating trifluoromethyl groups within the privileged 2-anilinoquinoline scaffold was designed, synthesized, and subjected to biological evaluation through a pharmacophore hybridization strategy. Upon evaluating the in vitro anti-cancer characteristics of the target compounds, it became clear that compound 8b, which contains a (4-(piperazin-1-yl)phenyl)amino substitution at the 2-position of the quinoline skeleton, displayed superior efficacy against four cancer cell lines by inducing apoptosis and cell cycle arrest. Following research conducted in a PC3 xenograft mouse model, it was found that compound 8b exhibited significant anti-cancer efficacy while demonstrating minimal toxicity. Additionally, the analysis of a 217-kinase panel pinpointed SGK1 as a potential target for this compound class with anti-cancer capabilities. This finding was further verified through molecular docking analysis and cellular thermal shift assays. To conclude, our results emphasize that compound 8b can be used as a lead compound for the development of anti-cancer drugs that target SGK1.

Ferroptosis in antitumor therapy: Unraveling regulatory mechanisms and immunogenic potential.

Ferroptosis, a recently discovered form of non-apoptotic cell death, has the potential to revolutionize anti-tumor therapy. This review highlights the regulatory mechanisms and immunogenic properties of ferroptosis, and how it can enhance the effectiveness of radio and immunotherapies in overcoming tumor resistance. However, tumor metabolism and the impact of ferroptosis on the tumor microenvironment present challenges in completely realizing its therapeutic potential. A deeper understanding of the effects of ferroptosis on tumor cells and their associated immune cells is essential for developing more effective tumor treatment strategies. This review offers a comprehensive overview of the relationship between ferroptosis and tumor immunity, and sheds new light on its application in tumor immunotherapy.

Shaping the immune-suppressive microenvironment on tumor-associated myeloid cells through tumor-derived exosomes.

Tumor-associated myeloid cells (TAMCs) play a crucial role in orchestrating the dynamics of the tumor immune microenvironment. This heterogeneous population encompasses myeloid-derived suppressor cells, tumor-associated macrophages and dendritic cells, all of which contribute to the establishment of an immunosuppressive milieu that fosters tumor progression. Tumor-derived exosomes (TEXs), small extracellular vesicles secreted by tumor cells, have emerged as central mediators in intercellular communication within the tumor microenvironment. In this comprehensive review, we explore the intricate mechanisms through which TEXs modulate immune-suppressive effects on TAMCs and their profound implications in cancer progression. We delve into the multifaceted ways in which TEXs influence TAMC functions, subsequently affecting tumor immune evasion. Furthermore, we elucidate various therapeutic strategies aimed at targeting TEX-mediated immune suppression, with the ultimate goal of bolstering antitumor immunity.

Apoptosis dysfunction: unravelling the interplay between ZBP1 activation and viral invasion in innate immune responses.

Apoptosis plays a pivotal role in pathogen elimination and maintaining homeostasis. However, viruses have evolved strategies to evade apoptosis, enabling their persistence within the host. Z-DNA binding protein 1 (ZBP1) is a potent innate immune sensor that detects cytoplasmic nucleic acids and activates the innate immune response to clear pathogens. When apoptosis is inhibited by viral invasion, ZBP1 can be activated to compensate for the effect of apoptosis by triggering an innate immune response. This review examined the mechanisms of apoptosis inhibition and ZBP1 activation during viral invasion. The authors outlined the mechanisms of ZBP1-induced type I interferon, pyroptosis and necroptosis, as well as the crosstalk between ZBP1 and the cGAS-STING signalling pathway. Furthermore, ZBP1 can reverse the suppression of apoptotic signals induced by viruses. Intriguingly, a positive feedback loop exists in the ZBP1 signalling pathway, which intensifies the innate immune response while triggering a cytokine storm, leading to tissue and organ damage. The prudent use of ZBP1, which is a double-edged sword, has significant clinical implications for treating infections and inflammation.

Possible hazards from biodegradation of soil plastic mulch: Increases in microplastics and CO2 emissions.

Biodegradable mulches are widely recognized as ecologically friendly substances. However, their degradation percentage upon entering soils may vary based on mulch type and soil microbial activities, raising concerns about potential increases in microplastics (MPs). The effects of using different types of mulch on soil carbon pools and its potential to accelerate their depletion have not yet well understood. Therefore, we conducted an 18-month experiment to investigate mulch biodegradation and its effects on CO2 emissions. The experiment included burying soil with biodegradable mulch made of polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT), and control treatments with traditional mulch (PE) and no mulch (CK). The results indicated that PE did not degrade, and the degradation percentage of PLA and PBAT were 46.2% and 88.1%, and the MPs produced by the degradation were 6.7 × 104 and 37.2 × 104 items/m2, respectively. Biodegradable mulch, particularly PLA, can enhance soil microbial diversity and foster more intricate bacterial communities compared to PE. The CO2 emissions were 0.58, 0.74, 0.99, and 0.86 g C/kg in CK, PE, PLA, , PBAT, respectively. A positive correlation was observed between microbial abundance and diversity with CO2 emissions, while a negative correlation was observed with soil total organic carbon. Biodegradable mulch enhanced the transformation of soil organic C into CO2 by stimulating microbial activity.

Design, synthesis and bioevaluation of novel prenylated chalcones derivatives as potential antitumor agents.

A series of novel prenylated chalcone derivatives with broad spectrum anticancer potential were designed and synthesized. Some of the synthesized target compounds showed potent anti-proliferative activities toward LNCaP (prostate cancer cell line), K562 (human leukemia cells), A549 (human lung carcinoma cell line) and HeLa (cervical cancer cell line) cell lines. Among of the active compounds, (E)-1-(4-(2-(diethylamino)ethoxy)-2-hydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(pyridin-3-yl)prop-2-en-1-one (C36) was directly interacted with protein kinase B (PKB), also known as AKT, significantly inhibited the pPI3K, pAKT(Ser473) protein levels to repress the growth of cancer cells by inducing apoptosis, arresting cell cycle. Our studies provide support for prenylated chalcone derivatives potential applications in cancer treatment as a potential AKT inhibitor.

P53 together with ferroptosis: a promising strategy leaving cancer cells without escape.

TP53, functioning as the keeper of the genome, assumes a pivotal function in the inhibition of tumorigenesis. Recent studies have revealed that p53 regulates ferroptosis pathways within tumor cells and is closely related to tumorigenesis. Therefore, we summarize the pathways and mechanisms by which p53 regulates ferroptosis and identify a series of upstream and downstream molecules involved in this process. Furthermore, we construct a p53-ferroptosis network centered on p53. Finally, we present the progress of drugs to prevent wild-type p53 (wtp53) degeneration and restore wtp53, highlighting the deficiencies of drug development and the prospects for p53 in cancer treatment. These findings provide novel strategies and directions for future cancer therapy.

Design, synthesis and bioevaluation of novel trifluoromethylquinoline derivatives as tubulin polymerization inhibitors.

Aim: A series of novel trifluoromethylquinoline derivatives were designed, synthesized and evaluated for antitumor activities. Methodology: All compounds were evaluated for antiproliferative activity against four human cancer cell lines. Results: Among them, 5a, 5m, 5o and 6b exhibited remarkable antiproliferative activities against all the tested cell lines at nanomolar concentrations. Mechanism of action studies demonstrated that 6b targeted the colchicine binding site, potentially inhibiting tubulin polymerization, and further studies indicated that 6b could arrest LNCaP cells in the G2/M phase and induce cell apoptosis. Molecular docking confirmed that 6b could bind to the colchicine binding site. Conclusion: Results suggested that 6b could serve as a promising lead compound for the development of novel tubulin polymerization inhibitors and cancer therapy.

The prevalence and factors associated with posttraumatic growth after 3-years outbreak of COVID-19 among resident physicians in China: a cross-sectional study.

Introduction: The Coronavirus disease 2019 (COVID-19) pandemic is a global traumatic event that has profoundly struck individuals' mental health. However, this might potentially promote positive transformation such as posttraumatic growth (PTG). Studies have indicated that the COVID-19 pandemic negatively affected the well-being of resident physicians, but little is known about PTG among this vulnerable population in China. Therefore, this study investigated the prevalence and associated factors of PTG among Chinese resident physicians after 3-years outbreak of COVID-19. Methods: An online survey was conducted from 9 March to 20 March in 2023. PTG was assessed using the 10-item Posttraumatic Growth Inventory-Short Form (PTGI-SF). Scores ≥30 implied moderate-to-high PTG. We also collected possible associated factors for PTG, including socio-demographic and psychological variables. Data was analyzed by applying descriptive statistics, univariable and multivariable logistic regression models. Results: In total, 2267 Chinese resident physicians provided validated data. 38.7% of them reported moderate-to-high PTG. In the multivariable logistic regression models, age (odds ratio, OR = 1.039; 95% confidence interval, 95%CI = 1.008-1.070), female (OR = 1.383, 95%CI = 1.151-1.662), satisfied or neutral with annual income (OR = 2.078, 95%CI = 1.524-2.832; OR = 1.416, 95%CI = 1.157-1.732), sufficient support at work (OR = 1.432, 95%CI = 1.171-1.751) and resilience (OR = 1.171, 95%CI = 1.096-1.252) were significantly positively associated with moderate-to-high PTG. On the contrary, burnout (OR = 0.653, 95%CI = 0.525-0.812), depression symptoms (OR = 0.700, 95%CI = 0.552-0.889), and stress (OR = 0.757, 95%CI = 0.604-0.949) were significantly negatively associated with moderate-to-high PTG. Discussion: Overall, resident physicians in China experienced relatively high prevalence of PTG that could be associated with several psychosocial factors. Findings may provide evidence to develop interventions for resident physicians to systematically and constructively process traumatic events related to the pandemic and foster their PTG.

Discovery of novel 2-(trifluoromethyl)quinolin-4-amine derivatives as potent antitumor agents with microtubule polymerization inhibitory activity.

In this work, a series of 2-(trifluoromethyl)quinolin-4-amine derivatives were designed and synthesized through structural optimization strategy as a microtubule-targeted agents (MTAs) and their cytotoxicity activity against PC3, K562 and HeLa cell lines were evaluated. The half maximal inhibitory concentration (IC50) of 5e, 5f, and 5o suggested that their potency of anti-proliferative activities against HeLa cell lines were better than the combretastatin A-4. Compound 5e showed the higher anti-proliferative activity against PC3, K562 and HeLa in vitro with IC50 values of 0.49 µM, 0.08 µM and 0.01 µM, respectively. Further mechanism study indicated that the representative compound 5e was new class of tubulin inhibitors by EBI competition assay and tubulin polymerization assays, it is similar to colchicine. Immunofluorescence staining revealed that compound 5e apparently disrupted tubulin network in HeLa cells, and compound 5e arrested HeLa cells at the G2/M phase and induced cells apoptosis in a dose-dependent manner. Molecular docking results illustrated that the hydrogen bonds of represented compounds reinforced the interactions in the pocket of colchicine binding site. Preliminary results suggested that 5e deserves further research as a promising tubulin inhibitor for the development of anticancer agents.

[Determination and Traceability Analysis of Phthalic Acid Esters in Garlic (Allium stivum L.) from Jiangsu Province, China].

Phthalic acid esters (PAEs) are ubiquitous environmental pollutants and are recognized as a threat to the environment and agricultural product safety across the world. In order to investigate the level of PAEs in garlic, soils, and agricultural films from Pizhou City, Jiangsu province, China, 11 garlic samples, 106 soil samples, and 4 agricultural film samples were collected and analyzed using GC-MS. In addition, the uptake and transport characteristics of six PAEs compounds classified as priority pollutants by the United States Environmental Protection Agency (EPA) in the garlic cultivar Daqingke were investigated under hydroponic conditions. The results indicated that dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) were the dominant PAEs species in garlic cloves of the different garlic varieties from Pizhou City. The average contents of DBP and DEHP in garlic cloves were 0.611 mg·kg-1 and 0.167 mg·kg-1, respectively, which were significantly higher than those of the commercial varieties of garlic. The concentrations of DBP and DEHP differed in three tissues of garlic bulbs, ordered as the skin of garlic bulb>skin of garlic clove>garlic clove. Dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DIBP), DBP, and DEHP were the main PAEs species and were detected in all the surface soils collected from Pizhou City. Compared with the soil allowable concentrations of the six PAEs in the United States, the DMP and DBP concentrations in approximately 100% and 63.2% of soil samples exceeded the recommended allowable concentrations set by the EPA. However, the levels of DEP, DIBP, and DEHP in the soils were below the maximum allowable concentrations set by the EPA. Nevertheless, the average content of DEHP in soils was 486 µg·kg-1 and was found to be much higher than that in the other four PAEs. Six PAEs, including DMP, DEP, DIBP, DBP, butyl benzyl phthalate (BBP), and DEHP, were detected in all the agricultural film samples. Among them, the contents of DBP and DEHP in the agricultural films were the highest, accounting for 53.7%-63.2% of the total PAEs. The amount of PAEs present in the residual film was significantly lower than that in the new film, and all six PAEs were detected in garlic or soil samples, suggesting that agricultural film can be an important source of PAEs in garlic farming soils and garlic. Furthermore, the garlic plants absorbed DMP and DEP efficiently from the substrate and showed higher translocation factors (TFs) for DMP and DEP than those for DBP, BBP, DEHP, and di-n-octyl phthalate (DnOP), resulting in a higher accumulation of DMP and DEP in the over-ground parts of garlic. In contrast, DBP and BBP in roots of garlic displayed higher bioconcentration factors (57.4 and 81.5, respectively) compared to those of the other four PAEs, whereas the TFs of DBP and BBP were lower; this may have contributed to the high accumulation of DBP in garlic bulbs. The BCFs and TFs of DEHP and DnOP in garlic were relatively lower, but the DEHP had been detected in all garlic cloves, which may be a result of the higher DEHP contents in soils.

Smallholder vegetable farming produces more soil microplastics pollution than large-scale farming.

Microplastics (MPs) accumulation in farmland has attracted global concern. Smallholder farming is the dominant type in China's agriculture. Compared with large-scale farming, smallholder farming is not constrained by restrictive environmental policies and public awareness about pollution. Consequently, the degree to which smallholder farming is associated with MP pollution in soils is largely unknown. Here, we collected soil samples from both smallholder and large-scale vegetable production systems to determine the distribution and characteristics of MPs. MP abundance in vegetable soils was 147.2-2040.4 MP kg-1 (averaged with 500.8 MP kg-1). Soil MP abundance under smallholder cultivation (730.9 MP kg-1) was twice that found under large-scale cultivation (370.7 MP kg-1). MP particle sizes in smallholder and large-scale farming were similar, and were mainly <1 mm. There were also differences in MP characteristics between the two types of vegetable soils: fragments (60%) and fibers (34%) were dominant under smallholder cultivation, while fragments (42%), fibers (42%), and films (11%) were dominant under large-scale cultivation. We observed a significant difference in the abundance of fragments and films under smallholder versus large-scale cultivation; the main components of MPs under smallholder cultivation were PP (34%), PE (28%), and PE-PP (10%), while these were PE (29%), PP (16%), PET (16%), and PE-PP (13%) under large-scale cultivation. By identifying the shape and composition of microplastics, it can be inferred that agricultural films were not the main MP pollution source in vegetable soil. We show that smallholder farming produces more microplastics pollution than large-scale farming in vegetable soil.

Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape.

Radiotherapy (RT) has been widely used in the clinical treatment of cancers, but radiotherapy resistance (RR) leads to RT failure, tumor recurrence and metastasis. Many studies have been performed on the potential mechanisms behind RR, and a strong link has been found between RR and DNA damage. RT-induced DNA damage triggers a protective mechanism called the DNA damage response (DDR). DDR consists of several aspects, including the detection of DNA damage and induction of cell cycle checkpoint, DNA repair, and eventual induction of cell death. A large number of studies have shown that DDR inhibition leads to significantly enhanced sensitivity of cancer cells to RT. DDR may be an effective target for radio- and chemo-sensitization during cancer treatment. Therefore, many inhibitors of important enzymes involved in the DDR have been developed, such as PARP inhibitors, DNA-PK inhibitors, and ATM/ATR inhibitors. In addition, DNA damage also triggers the cGAS-STING signaling pathway and the ATM/ATR (CHK)/STAT pathway to induce immune infiltration and T-cell activation. This review discusses the effects of DDR pathway dysregulation on the tumor response to RT and the strategies for targeting these pathways to increase tumor susceptibility to RT. Finally, the potential for the combination treatment of radiation, DDR inhibition, and immunotherapy is described.

Preoperative Vitamin D Level is Associated with Acute Pain After Video-Assisted Thoracoscopic Surgery: A Retrospective Cohort Study.

Purpose: Low vitamin D levels have been associated with musculoskeletal pain, cancer pain, chronic postoperative pain, and post-traumatic pain. However, their association with postoperative pain after video-assisted thoracoscopic surgery has not been explored. The aim of this study was to examine the association between vitamin D levels and postoperative pain after video-assisted thoracoscopic surgery. Patients and Methods: This study enrolled 194 adult patients who underwent elective non-cardiac thoracic surgery in Shanghai Pulmonary Hospital from February 2021 to June 2021. Following application of the exclusion criteria, 135 patients who underwent video-assisted thoracoscopic surgery were included in the final analysis. The primary outcome was the incidence of acute postoperative moderate-severe pain. Secondary outcomes included C-reactive protein (CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor-α levels in the immediate postoperative (48 hours) period, as well as pain scores at 3 months after surgery. A multivariable logistic regression model was used to analyze the association between vitamin D levels and acute postoperative moderate-severe pain. Results: Among 135 patients, 54.1% were categorized as having a low vitamin D level (<30 nmol/L). On multivariable analysis, patients with a low 25-hydroxy-vitamin D (25[OH]D) level had a higher risk of postoperative moderate-severe pain (odds ratio, 2.44; 95% confidence interval, 1.181-5.041; P = 0.016) when compared to patients with a sufficient 25(OH)D level. Static and dynamic pain scores at 3 months after surgery, as well as serum levels of CRP, IL-1, IL-6, and tumor necrosis factor-α were not significantly different between patients with low and sufficient 25(OH)D levels. Conclusion: Patients with low vitamin D levels are at a higher risk of acute moderate-severe pain after video-assisted thoracoscopic surgery. Trial Registration: http://www.chictr.org.cn, ChiCTR2100052380.

Optimization of the Heat Dissipation Performance of a Lithium-Ion Battery Thermal Management System with CPCM/Liquid Cooling.

In view of the harsh conditions of rapid charging and discharging of electric vehicles, a hybrid lithium-ion battery thermal management system combining composite phase change material (PCM) with liquid cooling was proposed. Based on the numerical heat transfer model, a simulation experiment for the battery thermal management system was carried out. Taking the maximum temperature and temperature difference of the battery module as the objectives, the effects of PCM thickness, the liquid flow rate and the cross-sectional area of the liquid channel on the temperature of the battery module were analyzed using response surface methodology (RSM). The results show that 31 groups of candidate parameter combinations can be obtained through response surface analysis, and phase change material (PCM) thickness should be minimized in order to improve space utilization in the battery module. The optimal parameter combination is a flow rate of 0.4 m/s and a PCM thickness of 5.58 mm, with the cross-sectional area of the liquid channel as 3.35 mm2.

New Insights into Hematopoietic Stem Cell Expansion to Stimulate Repopulation of the Adult Blood System for Transplantation.

Successful engraftment of hematopoietic stem cells (HSCs) and progenitor cells (HSPCs) may be considered as a basis for the repopulation of the blood cells after transplantation in adults. Therefore, in vivo and ex vivo expansion of HSCs holds great promise for clinical applications. In this review, the mechanisms of HSC expansion will be discussed, considering the previous studies and works of literature. This is aimed to identify the signaling pathways that regulate HSC expansion and improve the application of engraftment in disease management. The following aspects will be included: (i) Stimulation of HSCs growth in vivo through gene regulation and cytokines activation; (ii) direct or indirect induction of HSC expansion by regulating signaling pathways; (iii) addition to assisting cells to help in the proliferation of HSCs; (iv) changing of living environment in the HSCs cultures via adjusting components and forms of cultures; (v) enhancement of HSC expansion by incorporating substances, such as extracellular vesicles (EVs), UM171, among others. In this review, recent new findings that provide us with new insights into HSC expansion methods have been summarized. Furthermore, these findings will also provide more possibilities for the development of some novel strategies for expanding and engrafting HSCs applied for treatments of some hematopoietic disorders.

Sequence Requirements for miR-424-5p Regulating and Function in Cancers.

MiRNAs (microRNAs) are the most abundant family of small noncoding RNAs in mammalian cells. Increasing evidence shows that miRNAs are crucial regulators of individual development and cell homeostasis by controlling various biological processes. Therefore, miRNA dysfunction can lead to human diseases, especially in cancers with high morbidity and mortality worldwide. MiRNAs play different roles in these processes. In recent years, studies have found that miR-424-5p is closely related to the occurrence, development, prognosis and treatment of tumors. This review discusses how miR-424-5p plays a role in different kinds of cancers from different stages of tumors, including its roles in (i) promoting or inhibiting tumorigenesis, (ii) regulating tumor development in the tumor microenvironment and (iii) participating in cancer chemotherapy. This review provides a deep discussion of the latest findings on miR-424-5p and its importance in cancer, as well as a mechanistic analysis of the role of miR-424-5p in various tissues through target gene verification and pathway analysis.

Exosomes reveal the dual nature of radiotherapy in tumor immunology.

Radioresistance is the potential cause of cancer metastasis and recurrence. Radiation-induced changes in exosomes can partially explain the undesirable prognosis of radiotherapy (RT). Exosomes, newly discovered ways of cell communication, carry the characteristics of their origin, resulting in their diversity. Various exosomes in the tumor microenvironment exert different function in immune response. In this review, the dual effect of RT on the immune system was described, and the effect of radiotherapy on tumors via exosomes was explored. The molecules in exosomes after RT were described to play immunosuppressive and immunocompetent roles: immune-related receptors and cell signaling molecules involved in both adaptive and innate immune system were present. CD69, TIGIT, TIM-3, LAG-3 and the tumor necrosis factor (TNF) family that signal to T cells were shown to be regulated by exosomes after irradiation. The change in innate immunity-derived like receptors, Leukocyte Immunoglobin-Like Receptors (LILR) was described, as well as B7-H3, V-domain containing Ig suppressor of T cell activation (VISTA), and CD155 on tumor cells. These changed molecules inhibit and activate the immune system through different mechanisms. By analyzing the relationship between exosome-derived molecules and immunity, this review shows that radiotherapy can induce immunosuppression and immune clearance through exosomes, thereby treating tumors and improving patient prognosis.