TY - JOUR
T1 - Chemokine-mucinome interplay in shaping the heterogeneous tumor microenvironment of pancreatic cancer
AU - Ganguly, Koelina
AU - Shah, Ashu
AU - Atri, Pranita
AU - Rauth, Sanchita
AU - Ponnusamy, Moorthy P.
AU - Kumar, Sushil
AU - Batra, Surinder K.
N1 - Funding Information:
The authors/work on this manuscript were supported, in parts, by grants from the NIH R01 CA247471 , RO1 CA210637 , RO1 CA206444 , R01 CA228524 , R01 CA254036 , U01 CA210240 , PO1 CA217798 , and R44 CA235991 .
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/11
Y1 - 2022/11
N2 - Pancreatic cancer (PC) is exemplified by a complex immune-suppressive, fibrotic tumor microenvironment (TME), and aberrant expression of mucins. The constant crosstalk between cancer cells, cancer-associated fibroblasts (CAFs), and the immune cells mediated by the soluble factors and inflammatory mediators including cytokines, chemokines, reactive oxygen species (ROS) promote the dynamic temporal switch towards an immune-escape phenotype in the neoplastic cells and its microenvironment that bolsters disease progression. Chemokines have been studied in PC pathogenesis, albeit poorly in the context of mucins, tumor glycocalyx, and TME heterogeneity (CAFs and immune cells). With correlative analysis from PC patients’ transcriptome data, support from available literature, and scientific arguments-based speculative extrapolations in terms of disease pathogenesis, we have summarized in this review a comprehensive understanding of chemokine-mucinome interplay during stromal modulation and immune-suppression in PC. Future studies should focus on deciphering the complexities of chemokine-mediated control of glycocalyx maturation, immune infiltration, and CAF-associated immune suppression. Knowledge extracted from such studies will be beneficial to mechanistically correlate the mucin-chemokine abundance in serum versus pancreatic tumors of patients, which may aid in prognostication and stratification of PC patients for immunotherapy.
AB - Pancreatic cancer (PC) is exemplified by a complex immune-suppressive, fibrotic tumor microenvironment (TME), and aberrant expression of mucins. The constant crosstalk between cancer cells, cancer-associated fibroblasts (CAFs), and the immune cells mediated by the soluble factors and inflammatory mediators including cytokines, chemokines, reactive oxygen species (ROS) promote the dynamic temporal switch towards an immune-escape phenotype in the neoplastic cells and its microenvironment that bolsters disease progression. Chemokines have been studied in PC pathogenesis, albeit poorly in the context of mucins, tumor glycocalyx, and TME heterogeneity (CAFs and immune cells). With correlative analysis from PC patients’ transcriptome data, support from available literature, and scientific arguments-based speculative extrapolations in terms of disease pathogenesis, we have summarized in this review a comprehensive understanding of chemokine-mucinome interplay during stromal modulation and immune-suppression in PC. Future studies should focus on deciphering the complexities of chemokine-mediated control of glycocalyx maturation, immune infiltration, and CAF-associated immune suppression. Knowledge extracted from such studies will be beneficial to mechanistically correlate the mucin-chemokine abundance in serum versus pancreatic tumors of patients, which may aid in prognostication and stratification of PC patients for immunotherapy.
KW - Chemokines
KW - Glycans
KW - Mucins
KW - Pancreatic cancer
KW - Stroma
KW - Tumor-microenvironment
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U2 - 10.1016/j.semcancer.2022.03.022
DO - 10.1016/j.semcancer.2022.03.022
M3 - Review article
C2 - 35346803
AN - SCOPUS:85127369582
SN - 1044-579X
VL - 86
SP - 511
EP - 520
JO - Seminars in Cancer Biology
JF - Seminars in Cancer Biology
ER -