UBE2T promotes glioblastoma malignancy through ubiquitination-mediated degradation of RPL6.

Glioblastoma (GBM) is the most frequent and aggressive malignant glioma. Due to patients' poor prognosis, it is of great clinical significance to determine new targets that may improve GBM treatment. In the present study, we showed that ubiquitin (Ub)-conjugating enzyme E2T (UBE2T) was significantly overexpressed in GBM and could promote proliferation, invasion, and inhibit apoptosis of GBM cells. Mechanistically, UBE2T functioned as the Ub enzyme of ribosomal protein L6 (RPL6) and induced the ubiquitination and degradation of RPL6 in an E3 ligase-independent manner through direct modification by K48-linked polyubiquitination, thus contributing to the malignant progression of GBM cells. Furthermore, inhibiting the expression of RPL6 by UBE2T could not only reduce the expression of wild-type p53, but also enhance the gain-of-function of mutant p53. Moreover, knockdown of UBE2T in LN229 cells obviously suppressed tumor growth in LN229 xenograft mouse models. Collectively, our study demonstrated that UBE2T promotes GBM malignancy through ubiquitination-mediated degradation of RPL6 regardless of the p53 mutation status. It will provide new candidates for molecular biomarkers and therapeutic targets for clinical application in GBM.

Epstein-Barr virus-encoded latent membrane protein 1 promotes extracellular vesicle secretion through syndecan-2 and synaptotagmin-like-4 in nasopharyngeal carcinoma cells.

Increasing evidence indicates that extracellular vesicles (EVs) play an important role in cancer cell-to-cell communication. The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), which is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis, can trigger multiple cell signaling pathways that affect cell progression. Several reports have shown that LMP1 promotes EV secretion, and LMP1 trafficking by EVs can enhances cancer progression and metastasis. However, the molecular mechanism by which LMP1 promotes EV secretion is not well understood. In the present study, we found that LMP1 promotes EV secretion by upregulated syndecan-2 (SDC2) and synaptotagmin-like-4 (SYTL4) through nuclear factor (NF)-κB signaling in NPC cells. Further study indicated that SDC2 interacted with syntenin, which promoted the formation of the EVs, and SYTL4 is associated with the release of EVs. Moreover, we found that stimulation of EV secretion by LMP1 can enhance the proliferation and invasion ability of recipient NPC cells and tumor growth in vivo. In summary, we found a new mechanism by which LMP1 upregulates SDC2 and SYTL4 through NF-κB signaling to promote EV secretion, and further enhance cancer progression of NPC.

ADAM17 promotes the invasion of hepatocellular carcinoma via upregulation MMP21.

BACKGROUND: The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, however the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. So far, nothing is known about the relationship between ADAM17 and MMP21. METHODS: In this study, the expression level of ADAM17 and MMP21 in HCC tissues was measured by immunohistochemistry. The Scratch wounding assay and Transwell were used to identify the invasion and metastasis ability. ELISA was used to evaluate the production of MMP21. Coimmunoprecipitation experiments demonstrated a direct association between ADAM17 and MMP21. HPLC was used to confirmed that ADAM17 participated in the maturation of MMP21. RESULTS: Our present data indicated that ADAM17 and MMP21 was significantly upregulated in human HCC tissues. Knockdown of ADAM17 in HCC inhibited cell invasion and metastasis. Moreover, ADAM17 regulates the secretion and expression of MMP21. Furthermore we discovered a direct association between ADAM17 and MMP21, and we also found MMP21 prodomain could be cleaved by ADAM17. CONCLUSION: Our data suggest that ADAM17 plays an important role in the development of HCC invasion and metastasis and this function may be implement by MMP21.

Matrilin-2 prevents the TNFα-induced apoptosis of WB-F344 cells via suppressing JNK pathway.

Oval cells, a kind of hepatic progenitor cell quiescent at normal condition, activates to proliferate and differentiate into hepatocytes under severe and long-term liver injury, which usually raises severe inflammation. However, how oval cell survives in the inflammatory milieu interne is still unclear. Tumor necrosis factor α (TNFα), mimicking inflammatory hepatic milieu interne, was used to treat oval cell line, WB-F344, to test the protective function of matrilin-2. In this study, our data suggested that matrilin-2 prevented TNFα-induced apoptosis in WB-F344 cells via inhibiting ASK1/MKK7/JNK pathway. In conclusion, we determined that matrilin-2 plays the key role in maintaining the survival of oval cell and guarantees its proliferation under various injury factors.

A combined analysis of multi-omics data reveals the prognostic values and immunotherapy response of LAG3 in human cancers.

Lymphocyte-activation gene 3 (LAG3) is a highly anticipated immune checkpoint in the context of cancer, exerting regulatory control over immune cell proliferation and function to reinforce the advancement of cancers. However, the comprehensive functional analysis of LAG3 across various cancer types remains undisclosed; thus, this study aims to investigate the pan-cancer expression profile of LAG3. We have investigated the expression profile, prognostic significance, and genetic alterations of LAG3 in various cancers while elucidating its characteristic in immune response regulation. Our findings demonstrated that elevated LAG3 expression is significantly associated with favorable prognosis in patients with cutaneous melanoma (SKCM), and it may be a potential biomarker for SKCM. Furthermore, multiple immune algorithms have highlighted the important regulatory role of LAG3 for the tumor-infiltrating immune cells including CD8 + T cells, B cells, dendritic cells (DCs), macrophages, and natural killer (NK) cells. We also examined the distribution of LAG3 at the single-cell level and explored its functional significance. A comprehensive and systematic analysis of LAG3 would facilitate a comprehensive evaluation of LAG3 in cancer biology and provide valuable insights for cancer management.

Multi-omics analysis of DNA replication-associated primase polymerase (PRIMPOL) in pan-cancer: a potential target for prognosis and immune response.

BACKGROUND: It is critical to understand the mechanisms of human cancers in order to develop the effective anti-cancer therapeutic strategies. Recent studies indicated that primase polymerase (PRIMPOL) is strongly associated with the development of human cancers. Nevertheless, a systematic pan-cancer analysis of PRIMPOL remains to be further clarified. METHOD: Comprehensive multi-omics bioinformatics algorithms, such as TIMER2.0, GEPIA2.0 and cBioPortal, were utilized to evaluate the biological roles of PRIMPOL in pan-cancer, including the expression profiles, genomic alterations, prognostic values and immune regulation. RESULTS: PRIMPOL was upregulated in glioblastoma multiforme and kidney renal clear cell carcinoma. The brain lower grade glioma patients with enhanced PRIMPOL expression displayed poor prognostic values. We also demonstrated the PRIMPOL's immunomodulating effects on pan-cancer as well as its genomic changes and methylation levels. The aberrant expression of PRIMPOL was linked to various cancer-associated pathways, including DNA damage response, DNA repair, and angiogenesis, according to single-cell sequencing and function enrichment. CONCLUSIONS: This pan-cancer analysis offers a thorough review of the functional roles of PRIMPOL in human cancers, suggesting PRIMPOL as a potentially important biomarker for the progression and immunotherapy of various cancers.

Non-Coding RNAs Derived from Extracellular Vesicles Promote Pre-Metastatic Niche Formation and Tumor Distant Metastasis.

Metastasis is a critical stage of tumor progression, a crucial challenge of clinical therapy, and a major cause of tumor patient death. Numerous studies have confirmed that distant tumor metastasis is dependent on the formation of pre-metastatic niche (PMN). Recent studies have shown that extracellular vesicles (EVs) play an important role in PMN formation. The non-coding RNAs (ncRNAs) derived from EVs mediate PMN formation and tumor-distant metastasis by promoting an inflammatory environment, inhibiting anti-tumor immune response, inducing angiogenesis and permeability, and by microenvironmental reprogramming. Given the stability and high abundance of ncRNAs carried by EVs in body fluids, they have great potential for application in tumor diagnosis as well as targeted interventions. This review focuses on the mechanism of ncRNAs derived from EVs promoting tumor PMN formation and distant metastasis to provide a theoretical reference for strategies to control tumor metastasis.

Increased expression of FAT4 suppress metastasis of lung adenocarcinoma through regulating MAPK pathway and associated with immune cells infiltration.

FAT4 is an extremely large atypical cadherin with crucial roles in the control of planar cell polarity (PCP) and regulation of the Hippo signaling pathway. Our study aims to clarify the FAT4 expression patterns, as well as the significance of FAT4 in predicting the prognosis and cancer immunity to non-small cell lung cancer (NSCLC). FAT4 mRNA and protein expressions were both underregulated in NSCLC and associated with poor prognosis in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In addition, overexpress FAT4 with jujuboside A (JUA) or knockdown FAT4 with siRNA regulated the metastasis of LUAD through MAPK pathways. Moreover, the FAT4 expression included multiple immunological components to promote an immunosuppressive tumor microenvironment (TME). Furthermore, a study of the TCGA-LUAD cohort's DNA methylation results showed that most FAT4 DNA CpG sites were typically hypermethylated in NSCLC relative to the normal lung tissue. The DNA CpG sites cg25879360 and cg26389756 of FAT4 were found to be strongly associated with FAT4 expression in LUAD through the correlation study. In conclusion, this is the first to report the potential function of FAT4 in NSCLC. Hence, FAT4 could be used as a promising prognostic and immunological biomarker for NSCLC.

The implication of pyroptosis in cancer immunology: Current advances and prospects.

Pyroptosis is a regulated cell death pathway involved in numerous human diseases, especially malignant tumors. Recent studies have identified multiple pyroptosis-associated signaling molecules, like caspases, gasdermin family and inflammasomes. In addition, increasing in vitro and in vivo studies have shown the significant linkage between pyroptosis and immune regulation of cancers. Pyroptosis-associated biomarkers regulate the infiltration of tumor immune cells, such as CD4+ and CD8+ T cells, thus strengthening the sensitivity to therapeutic strategies. In this review, we explained the relationship between pyroptosis and cancer immunology and focused on the significance of pyroptosis in immune regulation. We also proposed the future application of pyroptosis-associated biomarkers in basic research and clinical practices to address malignant behaviors. Exploration of the underlying mechanisms and biological functions of pyroptosis is critical for immune response and cancer immunotherapy.

YAP1 synergize with YY1 transcriptional co-repress DUSP1 to induce osimertinib resistant by activating the EGFR/MAPK pathway and abrogating autophagy in non-small cell lung cancer.

YAP1 is a well-known core effector of the Hippo pathway in tumors, but its potential role in osimertinib resistance remained unexplored. Our study provides evidence that YAP1 acts as a potent promoter of osimertinib resistance. By inhibiting YAP1 with a novel inhibitor, CA3, and combining it with osimertinib, we observed a significant suppression of cell proliferation and metastasis, induction of apoptosis and autophagy, and a delay in the emergence of osimertinib resistance. Interestingly, CA3 combined with osimertinib executed its anti-metastasis and pro-tumor apoptosis in part through autophagy. Mechanistically, we found that YAP1, in collaboration with YY1, transcriptionally represses DUSP1, leading to the dephosphorylation of the EGFR/MEK/ERK pathway and YAP1 phosphorylation in osimertinib-resistant cells. Our results also validate that CA3, in combination with osimertinib, executes its anti-metastasis and pro-tumor apoptosis partly through autophagy and the YAP1/DUSP1/EGFR/MEK/ERK regulatory feedback loop in osimertinib-resistant cells. Remarkably, our findings illustrate that YAP1 protein is upregulated in patients after osimertinib treatment and osimertinib resistance. Overall, our study confirms that the YAP1 inhibitor CA3 increases DUSP1 with concomitant activation of the EGFR/MAPK pathway and induces autophagy to enhance the efficacy of third-generation EGFR-TKI treatments for NSCLC patients.

E3 ligase MAEA-mediated ubiquitination and degradation of PHD3 promotes glioblastoma progression.

Glioblastoma (GBM) is the most common malignant glioma, with a high recurrence rate and a poor prognosis. However, the molecular mechanism behind the malignant progression of GBM is still unclear. In the present study, through the tandem mass tag (TMT)-based quantitative proteomic analysis of clinical primary and recurrent glioma samples, we identified that aberrant E3 ligase MAEA was expressed in recurrent samples. The results of bioinformatics analysis showed that the high expression of MAEA was related to the recurrence and poor prognosis of glioma and GBM. Functional studies showed that MAEA could promote proliferation, invasion, stemness and temozolomide (TMZ) resistance. Mechanistically, the data indicated that MAEA targeted prolyl hydroxylase domain 3 (PHD3) K159 to promote its K48-linked polyubiquitination and degradation, thus enhancing the stability of HIF-1α, thereby promoting the stemness and TMZ resistance of GBM cells through upregulating CD133. The in vivo experiments further confirmed that knocking down MAEA could inhibit the growth of GBM xenograft tumors. In summary, MAEA enhances the expression of HIF-1α/CD133 through the degradation of PHD3 and promotes the malignant progression of GBM.

Dynamic m6A-ncRNAs association and their impact on cancer pathogenesis, immune regulation and therapeutic response.

Several types of modifications have been proven to participate in the metabolism and processing of different RNA types, including non-coding RNAs (ncRNAs). N-6-methyladenosine (m6A) is a dynamic and reversible RNA modification that is closely involved in the ncRNA homeostasis, and serves as a crucial regulator for multiple cancer-associated signaling pathways. The ncRNAs usually regulate the epigenetic modification, mRNA transcription and other biological processes, displaying enormous roles in human cancers. In this review, we summarized the significant implications of m6A-ncRNA interaction in various types of cancers. In particular, the interplay between m6A and ncRNAs in cancer pathogenesis and therapeutic resistance are being widely recognized. We also discussed the relevance of m6A-ncRNA interaction in immune regulation, followed by the interference on cancer immunotherapeutic procedures. In addition, we briefly highlighted the computation tools that could identify the accurate features of m6A methylome among ncRNAs. In summary, this review would pave the way for a better understanding of the biological functions of m6A-ncRNA crosstalk in cancer research and treatment.

Role of an Exosomes-Related lncRNAs Signature in Tumor Immune Microenvironment of Gastric Cancer.

Background: Exosomes plays a crucial role in intercellular communication of gastric cancer (GC), while long non-coding RNAs (lncRNAs) contributes to the tumorigenesis and progression of GC. This study aims to explore the prognostic exosomes-related lncRNAs of GC patients. Methods: Data of 375 GC patients were obtained from the TCGA database. The entire cohort was randomly divided into a training cohort and a validation cohort in a 2:1 ratio. Exosomes-related lncRNAs were identified by the Pearson correlation analysis with reported exosomes-related genes. LASSO Cox regression was used to construct the signature. Results: A prognostic signature consisting of 11 exosomes-related lncRNAs was identified, and patients with lower risk scores had a better prognosis than those with higher risk scores. ROC curves and multivariate Cox regression analysis showed that the signature was an independent risk factor for prognosis in both the training (HR: 3.254, 95% CI: 2.310-4.583) and validation cohorts (HR: 1.974, 95% CI: 1.108-3.517). Gene set enrichment analysis (GSEA) suggested associations between the signature and several immune-related pathways. The identified signature was shown to be associated with GC tumor microenvironment. The expression of two immune checkpoints was also increased in the high-risk group, including B7-H3 and VSIR, indicating the potential role of the identified signature in GC immunotherapies. Conclusion: A novel exosomes-related lncRNA signature, which may be associated with tumor immune microenvironment and potentially serve as an indicator for immunotherapy, has been identified to precisely predict the prognosis of GC patients.

The AlkB Family: Potential Prognostic Biomarkers and Therapeutic Targets in Glioblastoma.

The AlkB family of Fe (II) and α-ketoglutarate-dependent dioxygenases works by removing alkyl substituents from alkylation-damaged nucleic acid bases through oxidative dealkylation, subsequently affecting tumor progression and patient prognosis. However, the specific roles of the AlkB family in Glioblastoma remain to be elucidated. By taking advantage of the abundant bioinformatics databases, such as GEPIA2, cBioPortal and TIMER, we performed a comprehensive analysis of the AlkB family in GBM, and managed to identify the significant prognostic hallmarks and therapeutic targets within this family. We found that the expression levels of ALKBH2 and ALKBH8 were significantly up-regulated in GBM compared with normal tissues. Meanwhile, the patients with high levels of ALKBH2 and ALKBH8 possessed significant poor overall survival (OS). In addition, the results suggested that the biological function of the AlkB family was closely related to DNA damage repair, cell metabolism, cell proliferation and tumor immune infiltration in GBM. Furthermore, the high expression of ALKBH8 in GBM was verified by immunohistochemistry. Taken together, this study could provide meaningful information about the aberrant AlkB family associated with GBM initiation and progression, and help clinicians precisely predict patient survival and select alternative therapeutic drugs.

A pan-cancer analysis of copper homeostasis-related gene lipoyltransferase 1: Its potential biological functions and prognosis values.

As a key copper homeostasis-related molecule, lipoyltransferase 1 (LIPT1) is an essential enzyme for the activation of mitochondrial 2-ketoacid dehydrogenase, participating in fatty acylation. However, the biological significances of LIPT1 in the pan-cancer are unclear. Here, we comprehensively analyzed the functional characteristics of LIPT1 in human cancers and its roles in immune response. We found that LIPT1 was down-regulated in some cancers. And LIPT1 overexpression is associated with favorable prognosis in these patients, such as breast cancer, clear cell renal cell carcinoma, ovarian cancer and gastric cancer. We also explored the mutational status and methylation levels of LIPT1 in human cancers. Gene enrichment analysis indicated that abnormally expressed LIPT1 was significantly associated with immune cells infiltration, such as B cells, CD8+ T cells and cancer-associated fibroblast cells. The result from single cell sequencing reflected the important roles of LIPT1 in the regulation of several biological behaviors of cancer cells, such as DNA damage response and cell apoptosis. Taken together, our research could provide a comprehensive overview about the significances of LIPT1 in human pan-cancer progression, prognosis and immune.

Identification of Downregulated Exosome-Associated Gene ENPP1 as a Novel Lipid Metabolism and Immune-Associated Biomarker for Hepatocellular Carcinoma.

Exosome plays an important role in the occurrence and development of tumors, such as hepatocellular carcinoma (LIHC). However, the functions and mechanisms of exosome-associated molecules in LIHC are still underexplored. Here, we investigated the role of the exosome-related gene ENPP1 in LIHC. Comprehensive bioinformatics from multiple databases revealed that ENPP1 was significantly downregulated in LIHC tissues. The patients with downregulated ENPP1 displayed a poor prognosis. Immunohistochemistry (IHC) was used to further confirm the downregulated ENPP1 in LIHC tissues. In addition, the coexpression network of ENPP1 was also explored to understand its roles in the underlying signaling pathways, including fatty acid degradation and the PPAR signaling pathway. Simultaneously, GSEA analysis indicated the potential roles of ENPP1 in the lipid metabolism-associated signaling pathways in the pathogenesis of LIHC, including fatty acid metabolism, fatty acid synthesis, and so on. Finally, immunological analysis indicated that ENPP1 might also be involved in multiple immune-related features, including immunoinhibitors, immunostimulators, and chemokines. Taken together, these findings could enhance our understanding of ENPP1 in LIHC pathogenesis and immune response and provide a new target for ENPP1-related immunotherapy in clinical treatment.

Ferroptosis-Related Gene MT1G as a Novel Biomarker Correlated With Prognosis and Immune Infiltration in Colorectal Cancer.

Ferroptosis, a newly discovered way of cell death, has been proved to be involved in the oncogenesis and development of cancers, including colorectal cancer (CRC). Here, by identifying the differentially expressed genes (DEGs) from three CRC transcriptome microarray datasets (GSE20842, GSE23878, and GSE25070), we found that the expression of MT1G was significantly decreased in CRC tissues, and the patients with a high level of MT1G displayed a poor prognosis. Quantitative PCR (qPCR) further confirmed the downregulated MT1G in two CRC cells, HCT8 and HCT116. The colony-forming assay indicated that the MT1G overexpression exhibited a remarkable inhibition of cell proliferation in HCT8 and HCT116 cells. In addition, we explored the co-expressed genes of MT1G to gain a better understanding of its potential signaling pathways. Aberrantly expressed MT1G also affected the immune response of CRC patients. Collectively, these findings might deepen our comprehension on the potential biological implications of MT1G in CRC.

Identification and validation of a novel pyroptosis-related lncRNAs signature associated with prognosis and immune regulation of hepatocellular carcinoma.

Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes. However, research concerning pyroptosis-related lncRNAs in hepatocellular carcinoma (HCC) remains scarce. This study aims to explore the prognostic pyroptosis-related long non-coding RNAs (lncRNAs) of HCC patients. Data of 373 HCC patients were obtained from the TCGA database. The entire cohort was randomly divided into a training cohort and a validation cohort in a 2:1 ratio. Pyroptosis-related lncRNAs were identified by the Pearson correlation analysis with reported pyroptosis-related genes. LASSO Cox regression was used to construct the signature. A prognostic signature consisting of nine pyroptosis-related lncRNAs was identified, and patients with lower risk scores had a better prognosis than those with higher risk scores. Multivariate Cox regression analysis showed that the signature was an independent risk factor for prognosis in both the training and validation cohorts. In the training cohort, the area under the signature curve reached 0.8043 at 1-year, 0.7878 at 2-year, and 0.8118 at 3-year; in the validation cohort, it reached 0.7315 at 1-year, 0.7372 at 2-year, and 0.7222 at 3-year. Gene set enrichment analysis (GSEA) suggested associations between the signature and several immune-related pathways. The expression of multiple immune checkpoints was also increased in the high-risk group, including PD-1, PD-L1, CTLA4, B7-H3, VSIR, LAG3, and TIGIT. A novel pyroptosis-related lncRNA signature, which may be associated with tumor immunity and potentially serve as an indicator for immunotherapy, has been identified to precisely predict the prognosis of HCC patients.

Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis.

B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) is frequently altered in multiple cancer types, and BRAF V600 mutations act as a prime target for precision therapy. Although emerging evidence has investigated the role of BRAF, the comprehensive profiling of BRAF expression, alteration and clinical implications across various cancer types has not been reported. In this study, we used the TCGA dataset, covering 10,967 tumor samples across 32 cancer types, to analyze BRAF abnormal expression, DNA methylation, alterations (mutations and amplification/deletion), and their associations with patient survival. The results showed that BRAF expression, alteration frequency, mutation site distribution, and DNA methylation patterns varied tremendously among different cancer types. The expression of BRAF was found higher in PCPG and CHOL, and lower in TGCT and UCS compared to normal tissues. In terms of pathological stages, BRAF expression was significantly differentially expressed in COAD, KIRC, LUSC, and OV. The methylation levels of BRAF were significantly lower in LUSC, HNSC, and UCEC compared to normal tissue. The expression of BRAF and downstream gene (ETS2) was negatively correlated with methylation levels in various cancers. The overall somatic mutation frequency of BRAF was 7.7% for all cancer samples. Most fusion transcripts were found in THCA and SKCM with distinct fusion patterns. The majority of BRAF mutations were oncogenic and mainly distributed in the Pkinase_Tyr domain of THCA, SKCM, COADREAD, and LUAD. The BRAF mutations were divided into five levels according to the clinical targeted therapy implication. The results showed level 1 was mainly distributed in SKCM, COADREAD, and LUAD, while level 3B in THCA. The overall BRAF CNV frequency was about 42.7%, most of which was gain (75.9%), common in GBM, TGCT, and KIRP. In addition, the forest plot showed that increased BRAF expression was associated with poor patient overall survival in LIHC, OV, and UCEC. Taken together, this study provided a novel insight into the full alteration spectrum of BRAF and its implications for treatment and prognosis.

Decoding Roles of Exosomal lncRNAs in Tumor-Immune Regulation and Therapeutic Potential.

Exosomes are nanovesicles secreted into biofluids by various cell types and have been implicated in different physiological and pathological processes. Interestingly, a plethora of studies emphasized the mediating role of exosomes in the bidirectional communication between donor and recipient cells. Among the various cargoes of exosomes, long non-coding RNAs (lncRNAs) have been identified as crucial regulators between cancer cells and immune cells in the tumor microenvironment (TME) that can interfere with innate and adaptive immune responses to affect the therapeutic efficiency. Recently, a few major studies have focused on the exosomal lncRNA-mediated interaction between cancer cells and immune cells infiltrated into TME. Nevertheless, a dearth of studies pertains to the immune regulating role of exosomal lncRNAs in cancer and is still in the early stages. Comprehensive mechanisms of exosomal lncRNAs in tumor immunity are not well understood. Herein, we provide an overview of the immunomodulatory function of exosomal lncRNAs in cancer and treatment resistance. In addition, we also summarize the potential therapeutic strategies toward exosomal lncRNAs in TME.