Local and systemic immunosuppression in pancreatic cancer: Targeting the stalwarts in tumor’s arsenal

Mundry, Clara S.; Eberle, Kirsten C.; Singh, Pankaj K.; Hollingsworth, Michael A.; Mehla, Kamiya

doi:10.1016/j.bbcan.2020.188387

Cited by 29 publications

(25 citation statements)

References 172 publications

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“…The balance between pro-tumorigenic and anti-tumor factors in the microenvironment regulates tumor growth [ 77 ]. Cancer cells extensively communicate with stroma cells and convert them into allies from within, thus impacting diverse aspects of tumor biology [ 78 , 79 ]. On the one hand, tumor cells recruit stromal cells, inflammatory or/and immune cells, etc.…”

Section: Main Textmentioning

confidence: 99%

“…On the other hand, the stromal cells and inflammatory cells residing in TME have protection and supportive effects on the cancer cells. The interplay of tumor cells and non-tumor cells shapes the TME that allows tumor cells growth, invasion, and facilitates escaping the tumor immunosurveillance [ 78 , 79 ]. Failure of tumor immunosurveillance causes the clinical appearance of cancer and cancer progression.…”

Section: Main Textmentioning

confidence: 99%

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Pyroptosis: a new paradigm of cell death for fighting against cancer

Tan

Chen

et al. 2021

J Exp Clin Cancer Res

323

217

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Background Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer. Main body Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1β, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies. Conclusion In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy.

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Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Pyroptosis: a new paradigm of cell death for fighting against cancer

Tan

Chen

et al. 2021

J Exp Clin Cancer Res

323

217

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“…Pancreatic ductal adenocarcinomas (PDAC) are characterized by the capability to exercise a profound modification and inhibition of both the local and systemic immune response [ 23 ]. Thus, surgical procedures aimed at the removal of the primary tumour impact the immune status not only by mechanisms linked to the SII, but also by the consecutive lack of immunomodulating signals produced by the primary tumour.…”

Section: Discussionmentioning

confidence: 99%

Visceral Surgery Profoundly Affects the Cellular and Humoral Components of the Anti-Tumour Immune Response in a Murine Pancreatic Adenocarcinoma Model

Loening

Kleinwort

Partecke

et al. 2022

Cancers

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(1) Background: Surgery is the most important element of multimodal treatment concepts in oncological patients, especially in the early stages of pancreatic tumours. While the influence of primary tumour resection on the immune status was analysed in several studies, the impact of tumour-unrelated visceral surgery on the tumour-bearing organism and on the primary tumour itself is not yet fully understood. (2) Methods: We combined a murine model of orthotopically implanted adenocarcinoma of the pancreas with the model of surgically-induced immune dysfunction (SID). Mortality and general condition including body weight were observed over a period of 28 days. Tumour growth was analysed by MRI scans on days 8 and 27 following tumour implantation. On day 28, the immune cell populations in the blood and spleen as well as the serum cytokines were quantified. (3) Results: SID results in a significant deterioration of the general condition and a reduced increase in the body weight of tumour-bearing mice compared to the control groups, while mortality and tumour growth rate were not influenced. The numbers of spleen macrophages and neutrophils were increased in tumour-bearing animals following SID. Furthermore, both macrophage and neutrophil levels were increased in the peripheral blood. (4) Conclusions: The presented results might contribute to the basic understanding of the interaction of tumour and immune system and could contribute to new approaches to immunotherapeutic strategies.

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“…In contrast, larger particles normally remain at the vaccination site and are phagocytosed by the migratory APCs, which then migrate to the closest DLN 239 , 240 . PDAC is often characterized with strong local immunosuppression and distant immunoremodeling 241 , which renders ineffective antigen presentation by APCs and decreased co-stimulatory signaling to T cells. Systemic or intratumoral APC activation can be exploited to enhance T cell immunotherapy.…”

Section: Nanocarrier-driven Immunomodulatory Approaches For Pdacmentioning

confidence: 99%

Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

Liu¹,

Kshirsagar²,

Gautam³

et al. 2022

Theranostics

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Pancreatic tumors are highly desmoplastic and immunosuppressive. Delivery and distribution of drugs within pancreatic tumors are compromised due to intrinsic physical and biochemical stresses that lead to increased interstitial fluid pressure, vascular compression, and hypoxia. Immunotherapy-based approaches, including therapeutic vaccines, immune checkpoint inhibition, CAR-T cell therapy, and adoptive T cell therapies, are challenged by an immunosuppressive tumor microenvironment. Together, extensive fibrosis and immunosuppression present major challenges to developing treatments for pancreatic cancer. In this context, nanoparticles have been extensively studied as delivery platforms and adjuvants for cancer and other disease therapies. Recent advances in nanotechnology have led to the development of multiple nanocarrier-based formulations that not only improve drug delivery but also enhance immunotherapy-based approaches for pancreatic cancer. This review discusses and critically analyzes the novel nanoscale strategies that have been used for drug delivery and immunomodulation to improve treatment efficacy, including newly emerging immunotherapy-based approaches. This review also presents important perspectives on future research directions that will guide the rational design of novel and robust nanoscale platforms to treat pancreatic tumors, particularly with respect to targeted therapies and immunotherapies. These insights will inform the next generation of clinical treatments to help patients manage this debilitating disease and enhance survival rates.

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Local and systemic immunosuppression in pancreatic cancer: Targeting the stalwarts in tumor’s arsenal

Cited by 29 publications

References 172 publications

Pyroptosis: a new paradigm of cell death for fighting against cancer

Pyroptosis: a new paradigm of cell death for fighting against cancer

Visceral Surgery Profoundly Affects the Cellular and Humoral Components of the Anti-Tumour Immune Response in a Murine Pancreatic Adenocarcinoma Model

Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

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