Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment

Chin-King Looi, Felicia Fei-Lei Chung, Chee-Onn Leong, Shew-Fung Wong, Rozita Rosli, Chun-Wai Mai, Chin-King Looi, Felicia Fei-Lei Chung, Chee-Onn Leong, Shew-Fung Wong, Rozita Rosli, Chun-Wai Mai

Abstract

Background: Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in advanced pancreatic cancer patients. Compared with other cancers, pancreatic cancer exhibits remarkable resistance to conventional therapy and possesses a highly immunosuppressive tumor microenvironment (TME).

Main body: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME.

Conclusions: It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.

Keywords: Immunotherapy; Pancreatic cancer; Tumor microenvironment.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

This review does not contain any individual personal data and thus consent for publication is not applicable.

Competing interests

The authors declare that the review was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Figures

Fig. 1
Fig. 1
Crosstalk of pancreatic cancer cells with other cells in the tumor microenvironment
Fig. 2
Fig. 2
Frequency of mesothelin protein expression in various common solid malignancies

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