Role of different immune cells and metabolic pathways in modulating the immune response in pancreatic cancer (Review)

Elebo, N.; Fru, Pascaline; Omoshoro-Jones, J.; Candy, Geoffrey P.; Nweke, Ekene Emmanuel

doi:10.3892/mmr.2020.11622

Cited by 14 publications

(11 citation statements)

References 136 publications

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“…The tumor microenvironment of PC which consists of cells such as tumor-associated macrophages (TAMs), myofibroblasts, stromal cells, and cancer-associated fibroblasts (CAFs), is a key player in inducing chemoresistance (11)(12)(13)(14)(15)(16)(17)(18)(19). For example, CAFs have been implicated in drug resistance in pancreatic cancer via several mechanisms such as upregulating cytokine levels, blocking adequate delivery of drugs, activating tumorpromoting signaling pathways, increasing cell proliferation, promoting metastasis, and dysregulating cellular metabolism.…”

Section: Chemoresistance In Pdac: Role Of the Tumor Microenvironmentmentioning

confidence: 99%

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

et al. 2021

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Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance. Here we review the role of the individual growth factors in pancreatic cancer chemoresistance. Importantly, the interplay between the tumor microenvironment and chemoresistance is explored in the context of pivotal role played by growth factors. We further describe current and future potential therapeutic targeting of these factors.

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Section: Chemoresistance In Pdac: Role Of the Tumor Microenvironmentmentioning

confidence: 99%

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

et al. 2021

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“…Immune cells have dual roles in PDAC which are contributing to the tumour progression and paradoxically offering avenues for therapeutic intervention. The tumour microenvironment (TME) of PDAC is characterised by malignant cells, stromal components, and immune cells which converge in a delicate balance (7,8). Neutrophils play diverse roles in pancreatic cancer such as angiogenesis, progression, metastasis, and immunosuppression (9).…”

Section: Introductionmentioning

confidence: 99%

Comparative Immune profiling in Pancreatic Ductal Adenocarcinoma Progression Among South African patients

Elebo,

Abdel-Shafy,

Omoshoro-Jones

et al. 2023

Preprint

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Introduction: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate of only 11%. PDAC is characterized by an immunosuppressive microenvironment; thus, there have been multiple attempts to target it, although with little success. A better understanding of the immune landscape in PDAC is required to help elucidate the roles of these cells for effective targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients. Method: Blood samples were obtained from a total of 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC), 6 Chronic Pancreatitis (CP), and 6 healthy volunteers (HC). Immunophenotyping, real-time polymerase chain reactions (PCR), enzyme-linked immunosorbent assay (Elisa), and reactive oxygen species (ROS) assays were conducted. Statistical analysis was conducted in R (version 3.6.1) and Wilcoxon and Kruskal-Wallis rank-sum tests were used to compare between groups. Kaplan-Meier analysis and Spearman's rank test were used for survival and correlation analyses, respectively. Results: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD4+, CD8+, and CD3+CD4-CD8- T-cells increased across the group. Of note are the reduction of CD16+ NKTs across the RPC (p = 0.002), LAPC (p = 0.01), and MPC (p = 0.017) groups when compared to HC. Both NK (p = 0.0047) and NKTs (p = 0.0027) increased in RPC but decreased in both LAPC and MPC when compared to HC. Although there was no statistical correlation or differences observed when comparing the PDAC groups with the control groups, RPC had the highest foldchange for both CD4 and CD3 while the LAPC group had the highest fold change for CD8 and CD16 genes compared to MPC. The inflammatory status of PDAC was assessed by DEPPD levels of serum which were elevated in RPC (p = 0.003) and LAPC (p = 0.008) but decreased in MPC (p = 0.025), compared to the HC group. ROS was shown to be positively correlated with GlycA (R=0.45, p = 0.00096). Conclusion: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies.

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“…As a hallmark of cancer, tumour cells reprogram their metabolism, such as promoting glycolysis to maintain cell survival and increase proliferation rate [11][12][13]. Metabolites are products of the metabolism that navigate important biological functions such as energy conversion [14,15] and signalling [16,17]. Blood metabolite concentrations can reflect the metabolic adaptation of tumour or highlight the host response to the tumour [18].…”

Section: Introductionmentioning

confidence: 99%

Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.

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Role of different immune cells and metabolic pathways in modulating the immune response in pancreatic cancer (Review)

Cited by 14 publications

References 136 publications

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

Comparative Immune profiling in Pancreatic Ductal Adenocarcinoma Progression Among South African patients

Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry

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