Immunomodulation in Pancreatic Cancer

Krishnamoorthy, Mithunah; Lenehan, John; Burton, Jeremy P.; Vareki, Saman Maleki

doi:10.3390/cancers12113340

Cited by 13 publications

(9 citation statements)

References 76 publications

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“…Indeed, Tregs accumulate in tumors and the peripheral blood of patients with cancer. Tregs are recruited to tumors sites where they suppress antitumor cytotoxic response by binding to DCs and preventing them from activating CD8 + T cells [ 88 ], as summarized in Figure 2 . It has been demonstrated that Tregs contribute to inhibiting the immune response against PDAC cells, from the premalignant stage to invasive PDAC [ 89 ].…”

Section: Immunosuppressive Tme In Pdacmentioning

confidence: 99%

The Immune Landscape of Human Pancreatic Ductal Carcinoma: Key Players, Clinical Implications, and Challenges

Müller

Haghnejad

Schaefer

et al. 2022

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest cancer worldwide with an overall survival rate, all stages combined, of still <10% at 5 years. The poor prognosis is attributed to challenges in early detection, a low opportunity for radical resection, limited response to chemotherapy, radiotherapy, and resistance to immune therapy. Moreover, pancreatic tumoral cells are surrounded by an abundant desmoplastic stroma, which is responsible for creating a mechanical barrier, preventing appropriate vascularization and leading to poor immune cell infiltration. Accumulated evidence suggests that PDAC is impaired with multiple “immune defects”, including a lack of high-quality effector cells (CD4, CD8 T cells, dendritic cells), barriers to effector cell infiltration due to that desmoplastic reaction, and a dominance of immune cells such as regulatory T cells, myeloid-derived suppressor cells, and M2 macrophages, resulting in an immunosuppressive tumor microenvironment (TME). Although recent studies have brought new insights into PDAC immune TME, its understanding remains not fully elucidated. Further studies are required for a better understanding of human PDAC immune TME, which might help to develop potent new therapeutic strategies by correcting these immune defects with the hope to unlock the resistance to (immune) therapy. In this review, we describe the main effector immune cells and immunosuppressive actors involved in human PDAC TME, as well as their implications as potential biomarkers and therapeutic targets.

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Section: Immunosuppressive Tme In Pdacmentioning

confidence: 99%

The Immune Landscape of Human Pancreatic Ductal Carcinoma: Key Players, Clinical Implications, and Challenges

Müller

Haghnejad

Schaefer

et al. 2022

Cancers

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“…Different studies have proposed that the combination of immunotherapy with chemoradiotherapy promotes immunogenicity due to a decrease in immunoregulatory lymphocytes. It has been shown in pancreatic cancer that regulatory lymphocytes are present and are responsible for localized immunosuppression, and therefore limit the immune reaction (136)(137)(138). Moreover, another of the strategies proposed in recent years is the use of vaccines, where tumor antigens from neoplastic cells are used.…”

Section: Current Strategies With Immunotherapymentioning

confidence: 99%

Towards an updated view on the clinical management of pancreatic adenocarcinoma: Current and future perspectives (Review)

et al. 2021

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Pancreatic cancer has a dire prognosis and will represent the second leading cause of cancer death in the next 10 years. The multifactorial approach represents one of the main issues in controlling the extension of this neoplasm. In recent years, the characteristics of the tumor microenvironment, metastasis mechanisms and the relationship between immune system and neoplastic cells have been described, which has made it possible to understand the pathophysiology of pancreatic adenocarcinoma. Currently, there is a failure to provide an effective preventive method or early detection, so patients present with an advanced stage at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcome and in improving survival in long term. Therefore, in the recent years, diverse diagnostic tests, treatments and possible approaches have been developed in the fields of radiotherapy, chemotherapy and surgery to find a combination of them that improves life expectancy in patients diagnosed with pancreatic cancer. At the moment, numerous clinical trials are being conducted to evaluate preventive diagnostic procedures such as serological markers or perfecting available imaging tests. On the other hand, implementation of immunotherapy is being studied in a neoplasm that has lagged in the application of this procedure since present possible treatments do not substantially improve quality of life. Therefore, the purpose of our study is to summarize the main progresses that have been made in the diagnosis, treatment and screening of this disease, explaining the limitations that have been observed and analyzing future prospects in the management of this illness.

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“…Ideally, checkpoint inhibitors (CPI) exert anti-tumor effects by non-specific activation of T lymphocytes. However, studies have shown that the efficacy of immunotherapy based on CPI and CTLA-4 in PC treatment was not expected to be effective ( 101 ). Bradley and colleagues analyzed the tumor-associated peptides derived from 35 PDAC samples according to tandem MS ( 59 ).…”

Section: Ms and Treatment Of Pcmentioning

confidence: 99%

Application of Mass Spectrometry in Pancreatic Cancer Translational Research

Luo

Chen

et al. 2021

Front. Oncol.

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Pancreatic cancer (PC) is one of the most common malignant tumors in the digestive tract worldwide, with increased morbidity and mortality. In recent years, with the development of surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, and the change of the medical thinking model, remarkable progress has been made in researching comprehensive diagnosis and treatment of PC. However, the present situation of diagnostic and treatment of PC is still unsatisfactory. There is an urgent need for academia to fully integrate the basic research and clinical data from PC to form a research model conducive to clinical translation and promote the proper treatment of PC. This paper summarized the translation progress of mass spectrometry (MS) in the pathogenesis, diagnosis, prognosis, and PC treatment to promote the basic research results of PC into clinical diagnosis and treatment.

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Immunomodulation in Pancreatic Cancer

Cited by 13 publications

References 76 publications

The Immune Landscape of Human Pancreatic Ductal Carcinoma: Key Players, Clinical Implications, and Challenges

The Immune Landscape of Human Pancreatic Ductal Carcinoma: Key Players, Clinical Implications, and Challenges

Towards an updated view on the clinical management of pancreatic adenocarcinoma: Current and future perspectives (Review)

Application of Mass Spectrometry in Pancreatic Cancer Translational Research

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