Antibody therapy in pancreatic cancer: mAb-ye we’re onto something?

Boland, Anna; O'Kane, Anthony A; Buick, Richard; Longley, Daniel B.; Scott, Christopher J.

doi:10.1016/j.bbcan.2021.188557

Cited by 6 publications

(7 citation statements)

References 189 publications

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“…cancer.gov/) cohort; the GSE62452 (GEO, https://www.ncbi.nlm.nih.gov/geo/ ) cohort; The clinicopathologic data for all cohorts are displayed in Supplementary table 5. The TCGA public database that we downloaded contains mainly three types of pancreatic cancer data: Pancreas-Adenocarcinoma Ductal Type (150), Pancreas-Adenocarcinoma-Other Subtype [ 24 ], and Pancreas-Colloid (mucinous non-cystic) Carcinoma [ 4 ]. The raw single cell RNA sequence data presented in this paper have been deposited in the Genome Sequence Archive (CRA001160) at the National Genomics Data Center (NGDC) of the Chinese Academy of Sciences.…”

Section: Methodsmentioning

confidence: 99%

“…[ 3 ] With PBS or serum-free medium to blow the cell precipitation to the appropriate concentration, the general amount of subcutaneous tumor cells inoculated is 1–5 × 10 ^ 6 cells/mouse, the inoculated volume of 0.1 ml, so the cell suspension concentration of 1–5 × 10 ^ 7 cells/ml. [ 4 ] The cells should be inoculated as soon as possible after digestion in subcutaneous nude mice, generally trying to complete within half an hour, the way the cell suspension on ice reduces cell metabolism. [ 5 ] The choice of C57BL/6 mice is generally 5–8 weeks of age, planting site selection of blood-rich areas, such as the middle and rear armpits, and upper groin.…”

Section: Methodsmentioning

confidence: 99%

“…[ 3 ] For fresh solid tumor tissue, enzymatic, mechanical, or chemical dispersion can be employed to acquire a sufficient number of single cell suspensions. [ 4 ] The single cell suspension should contain no less than 107 cells/mL.…”

Section: Methodsmentioning

confidence: 99%

“…Its incidence rate and mortality have increased significantly in recent years. The early diagnosis rate of pancreatic cancer is not high, the operative mortality rate is high, and the cure rate is low [ 4 ]. Available treatment strategies for patients with PDAC include chemotherapy, surgical resection, radiotherapy, and immunotherapy [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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ABHD17C, a metabolic and immune-related gene signature, predicts prognosis and anti-PD1 therapy response in pancreatic cancer

Zhang

Xie

et al. 2023

Discov Onc

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Background PDAC is a highly malignant and immune-suppressive tumor, posing great challenges to therapy. Methods In this study, we utilized multi-center RNA sequencing and non-negative matrix factorization clustering (NMF) to identify a group of metabolism-related genes that could effectively predict the immune status and survival (both disease-free survival and overall survival) of pancreatic ductal adenocarcinoma (PDAC) patients. Subsequently, through the integration of single cell sequencing and our center's prospective and retrospective cohort studies, we identified ABHD17C, which possesses metabolic and immune-related characteristics, as a potential biomarker for predicting the prognosis and response to anti-PD1 therapy in PDAC. We then demonstrated how ABHD17C participates in the regulation of the immune microenvironment through in vitro glycolytic function experiments and in vivo animal experiments. Results Through screening for pancreatic cancer metabolic markers and immune status, we identified a critical molecule that inhibits pancreatic cancer survival and prognosis. Further flow cytometry analysis confirmed that ABHD17C is involved in the inhibition of the formation of the immune environment in PDAC. Our research found that ABHD17C participates in the metabolic process of tumor cells in in vitro and in vivo experiments, reshaping the immunosuppressive microenvironment by downregulating the pH value. Furthermore, through LDHA inhibition experiments, we demonstrated that ABHD17C significantly enhances glycolysis and inhibits the formation of the immune suppressive environment. In in vivo experiments, we also validated that ABHD17C overexpression significantly mediates resistance to anti-PD1 therapy and promotes the progression of pancreatic cancer. Conclusion Therefore, ABHD17C may be a novel and effective biomarker for predicting the metabolic status and immune condition of PDAC patients, and provide a potential predictive strategy for anti-PD1 therapy in PDAC.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

ABHD17C, a metabolic and immune-related gene signature, predicts prognosis and anti-PD1 therapy response in pancreatic cancer

Zhang

Xie

et al. 2023

Discov Onc

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“…Despite their high specificity and pharmacological advantages, monoclonal antibodies face several challenges in their application, such as off-target effects, limitations related to antibody size, and the risk of immune responses. To address these issues, various approaches have been explored, including humanization technology, Fc region modification, the design of drug delivery platforms targeting tumor cells, and the development of bispecific antibodies, all of which show promise [ 109 ].…”

Section: Treatment Options Targeting Tumors and Blood Vesselsmentioning

confidence: 99%

Clinical immunotherapy in pancreatic cancer

Ye,

Yu,

Zheng

et al. 2024

Cancer Immunol Immunother

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Pancreatic cancer remains a challenging disease with limited treatment options, resulting in high mortality rates. The predominant approach to managing pancreatic cancer patients continues to be systemic cytotoxic chemotherapy. Despite substantial advancements in immunotherapy strategies for various cancers, their clinical utility in pancreatic cancer has proven less effective and durable. Whether administered as monotherapy, employing immune checkpoint inhibitors, tumor vaccines, chimeric antigen receptors T cells, or in combination with conventional chemoradiotherapy, the clinical outcomes remain underwhelming. Extensive preclinical experiments and clinical trials in the realm of pancreatic cancer have provided valuable insights into the complexities of immunotherapy. Chief among the hurdles are the immunosuppressive tumor microenvironment, limited immunogenicity, and the inherent heterogeneity of pancreatic cancer. In this comprehensive review, we provide an overview and critical analysis of current clinical immunotherapy strategies for pancreatic cancer, emphasizing their endeavors to overcome immunotherapy resistance. Particular focus is placed on strategies aimed at reshaping the immunosuppressive microenvironment and enhancing T cell-mediated tumor cell killing. Ultimately, through deeper elucidation of the underlying pathogenic mechanisms of pancreatic cancer and the refinement of therapeutic approaches, we anticipate breakthroughs that will pave the way for more effective treatments in this challenging disease.

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