Dichotomous role of protein kinase A type I (PKAI) in the tumor microenvironment: a potential target for 'two-in-one' cancer chemoimmunotherapeutics.
An emerging trend in cancer chemoimmunotherapeutics is to develop 'two-in-one' therapies, which directly inhibit tumor growth and progression, as well as enhance anti-tumor immune surveillance. Protein kinase A (PKA) is a cAMP-dependent protein kinase that mediates signal transduction of G-protein coupled receptors (GPCRs). The regulatory subunit of PKA exists in two isoforms, RI and RII, which distinguish the PKA isozymes, PKA type I (PKAI) and PKA type II (PKAII). The differential expression of both PKA isozymes has long been linked to growth regulation and differentiation. RI/PKAI is particularly implicated in cellular proliferation and neoplastic transformation. Emerging experimental and pre-clinical data also indicate that RI/PKAI plays a key role in tumor-induced immune suppression. More briefly, RI/PKAI possesses a dichotomous role in the tumor microenvironment: not only contributes to tumor growth and progression, but also takes part in tumor-induced suppression of the innate and adaptive arms of anti-tumor immunosurveillance. This review specifically discusses this dichotomous role of RI/PKAI with respect to 'two-in-one' chemoimmunotherapeutic manipulation. The reviewed experimental and pre-clinical data provide the proof of concept validation that RI/PKAI may be regarded as an attractive target for a new, single-targeted, 'two hit' chemoimmunotherapeutic approach against cancer.
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Science Park, Guangzhou, 510530, China.
Muzammal
M
Hussain
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Science Park, Guangzhou, 510530, China.
Fei
F
Tang
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Science Park, Guangzhou, 510530, China.
Jinsong
J
Liu
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Science Park, Guangzhou, 510530, China; State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China. Electronic address: zhang_jiancun@gibh.ac.cn.
Jiancun
J
Zhang
Immunopharmacology Laboratory, Department of Pharmacology & Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
Aqeel
A
Javeed
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D007527:Isoenzymes / Q000502:physiology; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D019139:Tumor Escape; D059016:Tumor Microenvironment
D000970:Antineoplastic Agents; D007527:Isoenzymes; D017868:Cyclic AMP-Dependent Protein Kinases
AS-PKAI; Anti-tumor immunity; Chemoimmunotherapeutics; Immunosurveillance; Tumor reversion; ‘Two-in-one’