Immunotherapy for Pancreatic Cancer: Present and Future

Aroldi, Francesca; Zaniboni, Alberto

doi:10.2217/imt-2016-0142

Cited by 37 publications

(63 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, PT-112 stands out as a promising agent for the treatment of solid neoplasms that display limited sensitivity to ICBs and/or originate or tend to metastasize to the bone. [42][43][44][45] Based on our preclinical findings, it is tempting to speculate that PT-112 may cause a robust wave of ICD associated with an increased abundance of antigenic material from malignant cells as well as with the emission of chemotactic and immunostimulatory signals that altogether (re)activate anticancer immunity, de facto setting the stage for efficacious ICB-based immunotherapy. Additional experiments are required to validate this working model.…”

Section: Discussionmentioning

confidence: 98%

PT-112 induces immunogenic cell death and synergizes with immune checkpoint blockers in mouse tumor models

et al. 2020

View full text Add to dashboard Cite

PT-112 is a novel platinum-pyrophosphate conjugate under clinical development for cancer therapy. PT-112 mediates cytostatic and cytotoxic effects against a variety of human and mouse cancer cell lines in vitro. The cytotoxic response to PT-112 is associated with the emission of danger signals underpinning the initiation of anticancer immunity, including calreticulin exposure on the surface of dying cells, as well as ATP and HMGB1 secretion. Consistently, mouse cancer cells succumbing to PT-112 in vitro can be used to provide syngeneic, immunocompetent mice with immunological protection against a subsequent challenge with living tumor cells of the same type. Moreover, PT-112 administration synergizes with PD-1 or PD-L1 blockade in the control of mouse cancers in immunologically competent settings, as it simultaneously recruits immune effector cells and depletes immunosuppressive cells in the tumor microenvironment. Finally, PT-112 employed intratumorally in the context of immune checkpoint inhibition initiates a robust immune response that has systemic outreach and limits the growth of untreated, distant lesions. Thus, PT-112 induces the immunogenic demise of cancer cells, and hence stands out as a promising combinatorial partner of immune checkpoint blockers, especially for the treatment of otherwise immunologically cold tumors.

show abstract

Section: Discussionmentioning

confidence: 98%

PT-112 induces immunogenic cell death and synergizes with immune checkpoint blockers in mouse tumor models

et al. 2020

View full text Add to dashboard Cite

show abstract

“…However, the early stage of the disease is often asymptomatic, and GC is frequently diagnosed in the later stages, when it is characterized by invasion or metastasis. 4 However, patients with GC have not benefited from immunotherapy. 2 While cancers suppress the immune response by establishing a microenvironment, the immune cells decrease cancer immunogenicity in the process of tumorigenesis and cancer progression.…”

Section: Introductionmentioning

confidence: 99%

“…(range:[1][2][3][4][5][6][7][8][9][10][11][12]. The median score was used to determine the cut-off value of low or high CD28H expression.…”

mentioning

confidence: 99%

Overexpression of B7H5/CD28H is associated with worse survival in human gastric cancer

Chen

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Gastric cancer (GC) is a common malignancy with low 5-year overall survival (OS).Recently, immune therapy has been used to treat cancer. B7H5 and CD28H are novel immune checkpoint molecules. However, the prognostic value of B7H5/CD28H expression in patients with GC remains unclear. In this study, seventy-one patients diagnosed with GC were included in this study. Patients' GC tissues and matched adjacent tissue constructed a tissue microarray. The expression levels of B7H5 and CD28H were examined using immunohistochemistry. Correlations between the expression of B7H5 and CD28H and the clinical data were evaluated. We found that the expression of B7H5 and CD28H (both P = .001) were higher in GC tumour tissues than in adjacent noncancerous tissues. B7H5/CD28H expression acted as an independent predictive factor in the OS of patients with GC. High expression of B7H5 and CD28H predicted poor outcome.Patients in the B7H5+CD28H+ group had a lower 5-year OS compared with patients in the B7H5−CD28− group (4.5% vs 55.6%, P = .001). A significant difference was found in the 5-year OS between patients in the B7H5+CD28H− and B7H5+CD28H+ groups (33.5% vs 4.5%, P = .006). However, there was no correlation between B7H5 and CD28H expression (P = .844). Therefore, B7H5 and CD28H expression are up-regulated in GC and are independent prognostic factors for overall survival in patients with GC. Although there was no correlation between B7H5 and CD28H expression, high expression of B7H5 and CD28H predicts poor prognosis, especially when both are highly expressed. K E Y W O R D SB7 family checkpoints, B7H5, CD28H, gastric cancer, immunotherapy

show abstract

“…This low rate is partly because more than one-half of pancreatic cancer patients are diagnosed at a distant stage [ 2 ]. Although several treatment strategies including surgery of tumor resection, chemotherapy, and immunotherapy have been used, the outcomes of pancreatic cancer patients are still bad [ 3 , 4 ]. Thus, it is highly urgent to explore the molecular mechanism of pancreatic cancer progression and to find the new therapeutic targets for the treatment of pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA SPRY4-IT1 promotes cell proliferation and invasion by regulation of Cdc20 in pancreatic cancer cells

et al. 2018

View full text Add to dashboard Cite

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play a critical role in the development of human cancers including pancreatic cancer. Long non-coding RNA SPRY4-IT1 (sprouty4-intron transcript 1) has been reported to play an oncogenic role in various types of human carcinomas. However, the role of SPRY4-IT1 in pancreatic cancer is unclear. The objective of this study was to determine the function of SPRY4-IT1 on proliferation and invasion in pancreatic cancer. In the current study, we dissected the function and mechanism of SPRY4-IT1 by multiple approaches including Real-time RT-PCR, Western blotting analysis, MTT assay, Wound healing assay, Transwell assay, and transfection. We found that down-regulation of SPRY4-IT1 inhibited cell growth and induced cell apoptosis in pancreatic cancer cells. Moreover, SPRY4-IT1 knockdown induced cell cycle arrest at G0/G1 phase. Furthermore, inhibition of SPRY4-IT1 retarded cell migration and invasion in pancreatic cancer cells. Overexpression of SPRY4-IT1 enhanced cell growth and invasion, and inhibited cell apoptosis in pancreatic cancer cells. Mechanistically, suppression of SPRY4-IT1 inhibited the expression of Cdc20 in pancreatic cancer cells. Our findings demonstrated that inhibition of SPRY4-IT1 could be a potential therapeutic approach for the treatment of pancreatic cancer.

show abstract

Immunotherapy for Pancreatic Cancer: Present and Future

Cited by 37 publications

References 59 publications

PT-112 induces immunogenic cell death and synergizes with immune checkpoint blockers in mouse tumor models

PT-112 induces immunogenic cell death and synergizes with immune checkpoint blockers in mouse tumor models

Overexpression of B7H5/CD28H is associated with worse survival in human gastric cancer

Long non-coding RNA SPRY4-IT1 promotes cell proliferation and invasion by regulation of Cdc20 in pancreatic cancer cells

Contact Info

Product

Resources

About