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Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC. more...

ObjectiveBrain metastasis is a primary cause of morbidity and mortality in breast cancer patients. Therefore, elucidation and understanding of the underlying mechanisms are essential for the development of new therapeutic strategies.MethodsDifferential gene analysis was performed for those with and without distant metastasis in The Cancer Genome Atlas (TCGA) database and those with and without recurrence in the brain in the dataset GSE12276. The differentially expressed genes procured from the two databases were intersected to obtain the intersecting genes associated with brain metastasis. Thereafter, the intersecting genes were subjected to LASSO model construction to screen for prognostic genes. The expression of the obtained genes in metastatic breast cancer was observed, and survival analysis was performed. Finally, GSEA analysis of the obtained genes was performed, and the relationship between them and immune cells was explored.ResultsA total of 335 differential genes for the occurrence of distant metastases were obtained based on the TCGA database. A total of 1070 differential genes for recurrence to the brain were obtained based on the dataset GSE12276. The Venn diagram showed 24 intersecting genes associated with brain metastasis. The LASSO prognostic model contained a total of five genes (GBP2, GPR171, DIRAS3, RAC2, and CACNA1D). Expression difference analysis showed that GBP2, GPR171, DIRAS3, and RAC2 were significantly down-regulated in expression in metastatic breast cancer compared with primary breast cancer tumors. Only GPR171, DIRAS3, and RAC2 were strongly correlated with the overall survival of breast cancer patients. Their correlation analysis with immune cells showed that the correlation coefficient between the expression levels of DIRAS3 and immune cells was low, and the expression levels of GPR171 and RAC2 were more closely correlated with B cells and macrophages.ConclusionsThe expression of DIRAS3, GPR171 and RAC2, genes associated with brain metastasis, was reduced in metastatic breast cancer, and GPR171 was found to promote brain metastasis of breast cancer cells by inducing B cells and thereby. more...

BackgroundClinical target delineation is a primary focus in the field of radiotherapy. This study aimed to investigate whether high-risk clinical target volume can be removed in nasopharyngeal carcinoma patients with different T stages.Materials and methodsWe designed a test plan without the high-risk clinical target volume for 111 nasopharyngeal carcinoma patients and further compared the test plans with the treatment plans in the parameters of planning target volumes and the radiation dose to normal organs.ResultsOur data showed that when high-risk clinical target volume was abnegated, target coverage, conformity indices, and homogeneity indices of planning target volumes and doses of normal organs were not influenced in the T4 nasopharyngeal carcinoma patients, and more than 95% of the high-risk planning target volume area could still be covered by the 60 Gy dose line. However, only some T1–3 patients achieved the ideal dose coverage, and even fewer after induction chemotherapy (62.8% vs. 41.2%, p = 0.018). Gross tumor volume was positively correlated with the target coverage of the original high-risk planning target volume in the test-plan (p = 0.0001). Gross tumor volume can be used to predict whether the target coverage of high-risk planning target volume is more than 95% (area under the curve = 0.868).ConclusionOmitting high risk clinical target volume can be considered in patients with T4 nasopharyngeal carcinoma according to physical evaluations. However, this approach is only suitable for a specific subset of T1–3 patients. more...

The long non-coding RNA (lncRNA) ASAP1-IT1 has been recently shown to aberrantly increase in ovarian and bladder cancer, while its role in other malignancies remains unexplored. This study was to characterize the expression and assess the potential role of ASAP1-IT1 in hepatocellular carcinoma (HCC). Fifty-four paired HCC and histologically normal tissues were obtained from HCC patients. Human HCC cell lines (HepG2, Huh7, SMMC-7721, and BEL-7402) and a normal liver cell line (LO2) were used for in vitro studies. ASAP1-IT1-specific siRNAs were used to silence ASAP1-IT1 expression, while the pcDNA-ASAP1-IT1 vector was constructed to up-regulate its expression. In situ hybridization and qRT-PCR were performed to characterize subcellular localization and expression of ASAP1-IT1. Cell proliferation and migration assays were conducted to examine the role of ASAP1-IT1 in the progression of HCC. In silico analysis was conducted to predict putative miRNA binding sites, which were validated by luciferase reporter assays. ASAP1-IT1 levels were significantly increased in HCC tissues and cells compared with controls. Notably, higher ASAP1-IT1 levels were significantly associated with poorer prognosis of HCC patients. In situ hybridization analysis revealed that ASAP1-IT1 was mainly localized in the nucleus of hepatoma cells and differentially expressed in trabecular, compact, and pseudoglandular forms of liver cancer. Furthermore, knockdown of ASAP1-IT1 significantly suppressed cell proliferation and migration, while its overexpression significantly promoted cell proliferation and migration of HCC cells. Mechanistically, ASAP1-IT1 might exert its role in HCC progression, at least in part, by directly interacting with miR-221-3p. In conclusion, ASAP1-IT1 is abnormally elevated in HCC, and higher levels are correlated with poorer prognosis. An underlying mechanism has been proposed for ASAP1-IT1-associated promotion of proliferation and migration in HCC cells. These findings have provided evidence supporting the oncogenic role of ASAP1-IT1 in HCC. more...

Pathogen-based cancer therapies have been widely studied. Parasites, such as Toxoplasma gondii have elicited great interest in cancer therapy. Considering safety in clinical applications, we tried to develop an exosome-based immunomodulator instead of a live parasite for tumor treatment. The exosomes, called DC-Me49-exo were isolated from culture supernatants of dendritic cells (DCs) infected with the Me49 strain of T. gondii and identified. We assessed the antitumoral effect of these exosomes in a mouse model of colorectal cancer (CRC). Results showed that the tumor growth was significantly inhibited after treatment with DC-Me49-exo. Proportion of polymorphonuclear granulocytic bone marrow-derived suppressor cells (G-MDSCs, CD11b+Ly6G+) and monocytic myeloid-derived suppressor cells (M-MDSCs, CD11b+Ly6C+) were decreased in the DC-Me49-exo group compared with the control groups in vitro and in vivo. The proportion of DCs (CD45+CD11c+) increased significantly in the DC-Me49-exo group. Levels of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly decreased after treatment with DC-Me49-exo. Furthermore, we found that DC-Me49-exo regulated the lever of MDSC mainly by inhibiting the signal transducer and activator of transcription (STAT3) signaling pathway. These results indicated that exosomes derived from DCs infected with T. gondii could be used as part of a novel cancer therapeutic strategy by reducing the proportion of MDSCs. more...

Toxoplasma gondii is an obligate intracellular protozoan with anti-tumor activity against a variety of cancers. However, the therapeutic effect of T. gondii on colorectal cancer is unclear, and using direct Toxoplasma infection in immunotherapy involves safety concerns. This study investigated the anti-tumoral effect and mechanism of exosomes derived from dendritic cells (DCs) infected with T. gondii (Me49-DC-Exo). We used differential ultracentrifugation to isolate exosomes from uninfected DCs (DC-Exo) and T. gondii Me49-infected DCs (Me49-DC-Exo). The isolated exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Me49-DC-Exo significantly inhibited the tumor growth and reduced the proportion of M2 macrophages in the blood of tumor-bearing mice. In vitro, Me49-DC-Exo suppressed macrophage (RAW264.7) polarization to M2 phenotype. miRNA sequencing revealed that multiple miRNAs in Me49-DC-Exo were differentially expressed compared with DC-Exo, among which miR-182-5p, miR-155-5p, miR-125b-2-3p, and miR-155-3p were up-regulated, while miR-9-5p was significantly down-regulated. Transfecting mimics or inhibitors of these differential miRNAs into RAW264.7 cells showed that miR-155-5p promoted M1 macrophage polarization while inhibiting M2 macrophage polarization. Bioinformatics prediction and dual-luciferase reporter assay confirmed the suppressor of cytokine signaling 1 (SOCS1) as a direct target of miR-155-5p. Silencing SOCS1 gene expression in RAW264.7 cells increased CD86 + CD206 − M1 macrophage proportion, and inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels. However, arginase-1 and transglutaminase 2 expression levels decreased. These results suggest that the exosomes inhibit macrophage polarization to M2 phenotype and regulate SOCS1 expression by delivering functional miR-155-5p. These findings provide new ideas for colorectal cancer immunotherapy. more...

Located on chromosome 11q13.4, miR-139-5p has been confirmed by several studies as a possible attractive biomarker for cancer, including breast cancer, but its mechanism of correlation in different molecular subtypes of breast cancer has not been reported. In this study, comprehensive bioinformatics analysis was used to evaluate the expression of miR-139-5p in different molecular subtypes of breast cancer (luminal A, luminal B, HER2-enriched, and basal-like). The target genes of miR-139-5p were predicted by using an online database TargetScan and miRDB, and three key genes, FBN2, MEX3A, and TPD52, were screened in combination with differentially expressed genes in different molecular subtypes of breast cancer. The expression of the three genes was verified separately, and the genes were analyzed for pathway and functional enrichment. Bone marrow mesenchymal stem cells (BMSC) are another kind of highly plastic cell population existing in bone marrow besides hematopoietic stem cells. BMSC can affect the proliferation and migration of cancer cells, promote the metastasis and development of cancer, and regulate the tumor microenvironment by secreting exosome mirnas, thus affecting the malignant biological behavior of tumor cells. Finally, human bone marrow mesenchymal stem cells exosomes were obtained by ultracentrifugation, and the morphology of exosomes was observed by transmission electron microscopy. The expression of miR-139-5p in normal breast cells MCF-10A, human breast cancer cell line MDA-MB-231 cells, and BMSCs-derived exosomes were compared; the exosomes and MDA-MB-231 cells were co-cultured to observe their effects on the proliferation of the MDA-MB-231 cells. Human bone marrow mesenchymal stem cell-derived exosomes inhibited the growth of breast cancer cells and promoted the expression of FBN2, MEX3A, and TPD52 by transporting miR-139-5p. more...