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Long noncoding RNAs (lncRNAs) are a class of endogenous, non-protein coding RNAs that are highly linked to various cellular functions and pathological process. Emerging evidence indicates that lncRNAs participate in crosstalk between tumor and stroma, and reprogramming of tumor immune microenvironment (TIME). TIME possesses distinct populations of myeloid cells and lymphocytes to influence the immune escape of cancer, the response to immunotherapy, and the survival of patients. However, hitherto, a comprehensive review aiming at relationship between lncRNAs and TIME is missing. In this review, we focus on the functional roles and molecular mechanisms of lncRNAs within the TIME. Furthermore, we discussed the potential immunotherapeutic strategies based on lncRNAs and their limitations.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy. PDAC is only cured by surgical resection in its early stage, but there remains a relatively high possibility of recurrence. The development of PDAC is closely associated with the tumor microenvironment. Tumor-associated macrophages (TAMs) are one of the most abundant immune cell populations in the pancreatic tumor stroma. TAMs are inclined to M2 deviation in the tumor microenvironment, which promotes and supports tumor behaviors, including tumorigenesis, immune escape, metastasis, and chemotherapeutic resistance. Herein, we comprehensively reviewed the latest researches on the origin, polarization, functions, and reprogramming of TAMs in PDAC.

Background Gastric cancer (GC) is a common malignancy and frequent cause of cancer-related death. Long non-coding RNAs (lncRNAs) have emerged as important regulators and tissue-specific biomarkers of multiple cancers, including GC. Recent evidence has indicated that the novel lncRNA LINC01133 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in GC remain largely unknown. Methods LINC01133 expression was detected in 200 GC and matched non-cancerous tissues by quantitative reverse transcription PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of LINC01133 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, quantitative PCR arrays, TOPFlash/FOPFlash reporter assay, luciferase assay, and rescue experiments. Results LINC01133 was downregulated in GC tissues and cell lines, and its low expression positively correlated with GC progression and metastasis. Functionally, LINC01133 depletion promoted cell proliferation, migration, and the epithelial–mesenchymal transition (EMT) in GC cells, whereas LINC01133 overexpression resulted in the opposite effects both in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-106a-3p was a direct target of LINC01133, which functioned as a ceRNA in regulating GC metastasis. Mechanistic analysis demonstrated that miR-106a-3p specifically targeted the adenomatous polyposis coli (APC) gene, and LINC01133/miR-106a-3p suppressed the EMT and metastasis by inactivating the Wnt/β-catenin pathway in an APC-dependent manner. Conclusions Our findings suggest that reduced expression of LINC01133 is associated with aggressive tumor phenotypes and poor patient outcomes in GC. LINC01133 inhibits GC progression and metastasis by acting as a ceRNA for miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway, suggesting that LINC01133 may serve as a potential prognostic biomarker and anti-metastatic therapeutic target for GC.

In recent decades, immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy are two milestone achievements in clinical immunotherapy. However, both show limited efficacies in most solid neoplasms, which necessitates the exploration of new immunotherapeutic modalities. The failure of CAR-T and immune checkpoint blockade in several solid neoplasms is attributed to multiple factors, including low antigenicity of tumor cells, low infiltration of effector T cells, and diverse mechanisms of immunosuppression in the tumor microenvironment. New adoptive cell therapies have been attempted for solid neoplasms, including TCR-T, CAR-natural killer cells (CAR-NK), and CAR-macrophages (CAR-M). Compared to CAR-T, these new adoptive cell therapies have certain advantages in treating solid neoplasms. In this review, we summarized the 40-year evolution of adoptive cell therapies, then focused on the advances of TCR-T, CAR-NK, and CAR-M in solid neoplasms and discussed their potential clinical applications.

Surgery for metastatic pancreatic cancer remains controversial as the survival benefit is questionable. The aim of the present study was to analyze the survival of these patients using data extracted from the surveillance, epidemiology, and end results (SEER) program database. Further, studies on resection for metastatic disease to the lung were systematically reviewed. A total of 11,541 cases with synchronous distant metastasis were analyzed. The median survival of single-organ metastasis was better than of multi-organ metastasis (single-organ 4.0 ± 0.07 months, two-organs 3.0 ± 0.13 months, three/four-organs 2.0 ± 0.19 months; p < 0.0001). Single organ lung metastasis had longer median survival times compared to the other sites (lung 6.0 ± 0.32 months, HR 0.87, 95% CI 0.78–0.97; p = 0.013). Resection of the primary tumor was associated with longer survival in synchronous single-organ metastasis to the lung compared to no resection (14.0 ± 1.93 months vs 6.0 ± 0.31 months, p < 0.0001). A systematic literature review identified 79 cases of metachronous lung metastasis with a survival of 120.0 ± 6.32 months and 83.0 ± 24.84 months following resection of the primary tumor and metastasis, respectively. Lower TNM staging, longer interval to metastasis, and single metastatic lesion correlated with better survival. Resection in highly selected pancreatic cancer patients with synchronous and metachronous lung only metastasis might confer a survival benefit and should be considered on an individual basis.

The glycoprotein CD58, also known as lymphocyte-function antigen 3 (LFA-3), is a costimulatory receptor distributed on a broad range of human tissue cells. Its natural ligand CD2 is primarily expressed on the surface of T/NK cells. The CD2-CD58 interaction is an important component of the immunological synapse (IS) that induces activation and proliferation of T/NK cells and triggers a series of intracellular signaling in T/NK cells and target cells, respectively, in addition to promoting cell adhesion and recognition. Furthermore, a soluble form of CD58 (sCD58) is also present in cellular supernatant in vitro and in local tissues in vivo . The sCD58 is involved in T/NK cell-mediated immune responses as an immunosuppressive factor by affecting CD2-CD58 interaction. Altered accumulation of sCD58 may lead to immunosuppression of T/NK cells in the tumor microenvironment, allowing sCD58 as a novel immunotherapeutic target. Recently, the crucial roles of costimulatory molecule CD58 in immunomodulation seem to be reattracting the interests of investigators. In particular, the CD2-CD58 interaction is involved in the regulation of antiviral responses, inflammatory responses in autoimmune diseases, immune rejection of transplantation, and immune evasion of tumor cells. In this review, we provide a comprehensive summary of CD58 immunobiology.

The complement system has traditionally been considered a component of innate immunity against invading pathogens and “nonself” cells. Recent studies have demonstrated the immunoregulatory functions of complement activation in the tumor microenvironment (TME). The TME plays crucial roles in tumorigenesis, progression, metastasis and recurrence. Imbalanced complement activation and the deposition of complement proteins have been demonstrated in many types of tumors. Plasma proteins, receptors, and regulators of complement activation regulate several biological functions of stromal cells in the TME and promote the malignant biological properties of tumors. Interactions between the complement system and cancer cells contribute to the proliferation, epithelial-mesenchymal transition, migration and invasion of tumor cells. In this review, we summarize recent advances related to the function of the complement system in the TME and discuss the therapeutic potential of targeting complement-mediated immunoregulation in cancer immunotherapy.

Pancreatic cancer is an extremely dismal malignance. Chemotherapy has been widely applied to treat this intractable tumor. It has exclusive tumor microenvironment (TME), characterized by dense desmoplasia and profound infiltrations of immunosuppressive cells. Interactions between stromal cells and cancer cells play vital roles to affect the biological behaviors of pancreatic cancer. Targeting the stromal components of pancreatic cancer has shown promising results. In addition to the direct toxic effects of chemotherapeutic drugs on cancer cells, they can also remodel the TME, eventually affecting their efficacy. Herein, we reviewed the following four aspects; (1) clinical landmark advances of chemotherapy in pancreatic cancer, since 2000; (2) interactions and mechanisms between stromal cells and pancreatic cancer cells; (3) remodeling effects and mechanisms of chemotherapy on TME; (4) targeting stromal components in pancreatic cancer.

Traditionally, immunoglobulin (Ig) was believed to be produced by only B-lineage cells. However, increasing evidence has revealed a high level of Ig expression in cancer cells, and this Ig is named cancer-derived Ig. Further studies have shown that cancer-derived Ig shares identical basic structures with B cell-derived Ig but exhibits several distinct characteristics, including restricted variable region sequences and aberrant glycosylation. In contrast to B cell-derived Ig, which functions as an antibody in the humoral immune response, cancer-derived Ig exerts profound protumorigenic effects via multiple mechanisms, including promoting the malignant behaviors of cancer cells, mediating tumor immune escape, inducing inflammation, and activating the aggregation of platelets. Importantly, cancer-derived Ig shows promising potential for application as a diagnostic and therapeutic target in cancer patients. In this review, we summarize progress in the research area of cancer-derived Ig and discuss the perspectives of applying this novel target for the management of cancer patients.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.