Inflammation and Pancreatic Cancer: Focus on Metabolism, Cytokines, and Immunity

Padoan, Andrea; Plebani, Mario; Basso, Daniela

doi:10.3390/ijms20030676

Cited by 264 publications

(245 citation statements)

References 117 publications

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“…However, it is known that PDAC is an inflammatory cancer and patients show an increase in a certain number of cytokines, including IL-6. The consequence is an inflammation, mediated mainly by IL-6, locally generating an immunosuppressive microenvironment responsible for the escape of tumor cells and their dissemination [25]. PDT using the new PS seems to counterbalance this effect.…”

Section: Discussionmentioning

confidence: 99%

An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

Quilbé

Moralès

Baydoun

et al. 2020

JCM

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To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

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Section: Discussionmentioning

confidence: 99%

An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

Quilbé

Moralès

Baydoun

et al. 2020

JCM

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“…As a result of this, they produce an immune response via pro-inflammatory cytokines release, such as IL-6, IL-1β, TNF, and IFN-γ, and these inflammatory markers might act in nearby (paracrine action) or distant tissues (endocrine action). Likewise, the tumor microenvironment releases cytokines that contribute to their growth and favor the energy supply for them [45]. Based on this context, this section aims to describe the inflammatory pathways within skeletal muscle that may lead to muscle wasting.…”

Section: Inflammatory Markers and Muscle Massmentioning

confidence: 99%

Cancer Cachexia and Related Metabolic Dysfunction

Fonseca

Farkaš

Dora

et al. 2020

IJMS

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Cancer cachexia is a complex multifactorial syndrome marked by a continuous depletion of skeletal muscle mass associated, in some cases, with a reduction in fat mass. It is irreversible by nutritional support alone and affects up to 74% of patients with cancer—dependent on the underlying type of cancer—and is associated with physical function impairment, reduced response to cancer-related therapy, and higher mortality. Organs, like muscle, adipose tissue, and liver, play an important role in the progression of cancer cachexia by exacerbating the pro- and anti-inflammatory response initially activated by the tumor and the immune system of the host. Moreover, this metabolic dysfunction is produced by alterations in glucose, lipids, and protein metabolism that, when maintained chronically, may lead to the loss of skeletal muscle and adipose tissue. Although a couple of drugs have yielded positive results in increasing lean body mass with limited impact on physical function, a single therapy has not lead to effective treatment of this condition. Therefore, a multimodal intervention, including pharmacological agents, nutritional support, and physical exercise, may be a reasonable approach for future studies to better understand and prevent the wasting of body compartments in patients with cancer cachexia.

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“…There are other unmentioned immune deviations related to PaCa. We recommend overviews focusing on cytokines and chemokines (736)(737)(738)(739) and additional immunosuppressive molecules (740), where we only mention a few. RIP1 and 3 1 , highly expressed in PaCa, are key mediators of necroptosis, a caspase-independent cell death.…”

Section: Tregmentioning

confidence: 99%

“…The dectin1-galectin9 axis is central in directing the differentiation of TAM to a M2like phenotype, which suffices for reprogramming CD4+ and CD8+ T-cells (749). Finally, we list some reviews helpful as starting information on PaCa-selective metabolic changes that affect immune responses in PaCa (739,(750)(751)(752)(753)(754).…”

Section: Tregmentioning

confidence: 99%