TY - JOUR
T1 - Local and systemic immunosuppression in pancreatic cancer
T2 - Targeting the stalwarts in tumor's arsenal
AU - Mundry, Clara S.
AU - Eberle, Kirsten C.
AU - Singh, Pankaj K.
AU - Hollingsworth, Michael A.
AU - Mehla, Kamiya
N1 - Funding Information:
This study was funded in part by the support of grants from the National Institutes of Health grant, USA ( R01CA210439 , R01CA163649 , and R01CA216853 , NCI) to PKS, the Specialized Programs for Research Excellence; NCI-SPORE, USA ( 2P50 CA127297 ) to MAH and PKS, and the Pancreatic Cancer detection Concortium; NCI-PCDC, USA ( 5U01CA210240) to MAH. KM is supported by NCI-SPORE, USA ( P50 CA127297) Career Development Award.
Publisher Copyright:
© 2020 The Authors
PY - 2020/8
Y1 - 2020/8
N2 - Late detection, compromised immune system, and chemotherapy resistance underlie the poor patient prognosis for pancreatic ductal adenocarcinoma (PDAC) patients, making it the 3rd leading cause of cancer-related deaths in the United States. Cooperation between the tumor cells and the immune system leads to the immune escape and eventual establishment of the tumor. For more than 20 years, sincere efforts have been made to intercept the tumor-immune crosstalk and identify the probable therapeutic targets for breaking self-tolerance toward tumor antigens. However, the success of these studies depends on detailed examination and understanding of tumor-immune cell interactions, not only in the primary tumor but also at distant systemic niches. Innate and adaptive arms of the immune system sculpt tumor immunogenicity, where they not only aid in providing an amenable environment for their survival but also act as a driver for tumor relapse at primary or distant organ sites. This review article highlights the key events associated with tumor-immune communication and associated immunosuppression at both local and systemic microenvironments in PDAC. Furthermore, we discuss the approaches and benefits of targeting both local and systemic immunosuppression for PDAC patients. The present articles integrate data from clinical and genetic mouse model studies to provide a widespread consensus on the role of local and systemic immunosuppression in undermining the anti-tumor immune responses against PDAC.
AB - Late detection, compromised immune system, and chemotherapy resistance underlie the poor patient prognosis for pancreatic ductal adenocarcinoma (PDAC) patients, making it the 3rd leading cause of cancer-related deaths in the United States. Cooperation between the tumor cells and the immune system leads to the immune escape and eventual establishment of the tumor. For more than 20 years, sincere efforts have been made to intercept the tumor-immune crosstalk and identify the probable therapeutic targets for breaking self-tolerance toward tumor antigens. However, the success of these studies depends on detailed examination and understanding of tumor-immune cell interactions, not only in the primary tumor but also at distant systemic niches. Innate and adaptive arms of the immune system sculpt tumor immunogenicity, where they not only aid in providing an amenable environment for their survival but also act as a driver for tumor relapse at primary or distant organ sites. This review article highlights the key events associated with tumor-immune communication and associated immunosuppression at both local and systemic microenvironments in PDAC. Furthermore, we discuss the approaches and benefits of targeting both local and systemic immunosuppression for PDAC patients. The present articles integrate data from clinical and genetic mouse model studies to provide a widespread consensus on the role of local and systemic immunosuppression in undermining the anti-tumor immune responses against PDAC.
KW - Bone marrow
KW - Checkpoint inhibitors
KW - Lymph nodes
KW - Pancreatic cancer
KW - Spleen
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U2 - 10.1016/j.bbcan.2020.188387
DO - 10.1016/j.bbcan.2020.188387
M3 - Review article
C2 - 32579889
AN - SCOPUS:85086783025
SN - 0304-419X
VL - 1874
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
IS - 1
M1 - 188387
ER -