Open AccessPD-1/PD-L1 expression in pancreatic cancer and its implication in novel therapies
Author(s) -
Adrian Mucileanu,
Romeo Chira,
Petru Adrian Mircea
Publication year - 2021
Publication title -
medicine and pharmacy reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.35
H-Index - 16
eISSN - 2668-0572
pISSN - 2602-0807
DOI - 10.15386/mpr-2116
Subject(s) - pancreatic cancer , immunotherapy , cancer research , microsatellite instability , immune system , cancer , effector , tumor microenvironment , medicine , carcinogenesis , antigen , cancer immunotherapy , dna mismatch repair , immunology , biology , colorectal cancer , microsatellite , allele , biochemistry , gene
Pancreatic cancer is the seventh leading cause of death in developed countries and it still has a poor prognosis despite intense research in the last 20 years. Immunotherapy is a relatively new strategy in cancer treatment. The aim of immunotherapy is to block the immunosuppressive effect of tumoral cells. The PD1/PD-L1 axis has an important role in the inhibition of effector T cells and the development of regulatory T cells (Tregs). Blocking these checkpoints, and also inhibitory signals, leads to apoptosis of Tregs and increased immune response of effector T cells against tumoral antigens. Unfortunately, pancreatic cancer is generally considered to be a non-immunogenic tumor. Thus PD-1/PD-L1 inhibitors demonstrated poor results in pancreatic cancer, excepting some patients with MSI/dMMR (microsatellite instability/deficient mismatch repair). Furthermore, pancreatic cancer has a particular microenvironment with a strong desmoplastic reaction, increased interstitial fluid pressure, hypoxic conditions, and acidic extracellular pH, which promote tumorigenesis and progression of the tumor. Mismatch repair deficiency (dMMR) is correlated with a high level of mutation-associated neoantigens, most recognized by immune cells which could predict a favorable response to anti-PD-1/PD-L1 therapy. PD-1/PD-L1 molecules could be also found as soluble forms (sPD-1, sPD-L1). These molecules have a potential role in the prognosis and treatment of pancreatic cancer.