Immunomodulation in Pancreatic Cancer

Mithunah Krishnamoorthy; John G Lenehan; Jeremy P Burton; Saman Maleki Vareki

doi:10.3390/cancers12113340

Immunomodulation in Pancreatic Cancer

Cancers (Basel). 2020 Nov 12;12(11):3340. doi: 10.3390/cancers12113340.

Authors

Mithunah Krishnamoorthy^{1

2}, John G Lenehan³, Jeremy P Burton^{1

4

5}, Saman Maleki Vareki^{2

6

7}

Affiliations

¹ Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 3K7, Canada.
² Cancer Research Laboratory Program, Lawson Health Research Institute, London, ON N6A 5W9, Canada.
³ Division of Medical Oncology, Department of Oncology, University of Western Ontario, London, ON N6A 3K7, Canada.
⁴ Canadian Centre for Human Microbiome and Probiotics, Lawson Health Research Institute, London, ON N6A 4V2, Canada.
⁵ Division of Urology, Department of Surgery, University of Western Ontario, London, ON N6A 3K7, Canada.
⁶ Department of Pathology and Laboratory Medicine, University of Western Ontario, London, ON N6A 3K7, Canada.
⁷ Division of Experimental Oncology, Department of Oncology, University of Western Ontario, London, ON N6A 3K7, Canada.

Abstract

Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.

Keywords: T-cells; anti-PD1; fecal microbiota transplant; immunotherapy; microbiome; pancreatic cancer; pancreatic ductal carcinoma.

Publication types

Review

Grants and funding

N/A/London Regional Cancer Program's Catalyst Grant Program, Keith Smitt Translational Research Grants.