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    Immunotherapy, radiotherapy, and hyperthermia: A combined therapeutic approach in pancreatic cancer treatment

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    Author
    Mahmood, J.
    Shukla, H.D.
    Soman, S.
    Date
    2018
    Journal
    Cancers
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.3390/cancers10120469
    Abstract
    Pancreatic cancer (PC) has the highest mortality rate amongst all other cancers in both men and women, with a one-year relative survival rate of 20%, and a five-year relative survival rate of 8% for all stages of PC combined. The Whipple procedure, or pancreaticoduodenectomy, can increase survival for patients with resectable PC, however, less than 20% of patients are candidates for surgery at time of presentation. Most of the patients are diagnosed with advanced PC, often with regional and distant metastasis. In these advanced cases, chemotherapy and radiation have shown limited tumor control, and PC continues to be refractory to treatment and results in a poor survival outcome. In recent years, there has been intensive research on checkpoint inhibitor immunotherapy for PC, however, PC is characterized with dense stromal tissue and a tumor microenvironment (TME) that is highly immunosuppressive, which makes immunotherapy less effective. Interestingly, when immunotherapy is combined with radiation therapy (RT) and loco-regional hyperthermia (HT), it has demonstrated enhanced tumor responses. HT improves tumor killing via a variety of mechanisms, targeting both the tumor and the TME. Targeted HT raises the temperature of the tumor and surrounding tissues to 42–43 °C and makes the tumor more immunoresponsive. HT can also modulate the immune system of the TME by inducing and synthesizing heat shock proteins (HSP), which also activate an anti-tumor response. It is well known that HT can enhance RT-induced DNA damage in cancer cells and simultaneously help to oxygenate hypoxic regions. Thus, it is envisaged that combined HT and RT might have immunomodulatory effects in the PC-TME, making PC more responsive to immunotherapies. Moreover, the combined tripartite approach of immunotherapy, RT, and HT could reduce the overall toxicity associated with each individual therapy, while concomitantly enhancing the immunotherapeutic effect of overall individual therapies to treat local and metastatic PC. Thus, the use of a tripartite combinatorial approach could be promising and more efficacious than monotherapy or dual therapy to treat and increase the survival of the PC patients. Copyright 2018 by the authors. Licensee MDPI, Basel, Switzerland.
    Sponsors
    Seed grant from Department of Radiation Oncology, University of Maryland, Baltimore, School of Medicine and a partial grant from the William & Ella Owens Medical Research Foundation.
    Keyword
    Immunotherapy
    Metastasis
    Pancreatic cancer
    Radiation therapy
    Targeted hyperthermia
    Tripartite
    Tumor microenvironment
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85058495868&doi=10.3390%2fcancers10120469&partnerID=40&md5=58417444a3fafca6c8b08d7b66dcdb5f; http://hdl.handle.net/10713/9397
    ae974a485f413a2113503eed53cd6c53
    10.3390/cancers10120469
    Scopus Count
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    UMB Open Access Articles 2018

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