title: Prostate cancer and immunoproteome: awakening and reprogramming the guardian angels.
abstract: Prostate cancer is a life-threatening molecular disorder that is undruggable to date because of stumbling blocks in the standardization of therapy. An emerging framework of research is addressing how pathways that are derailed during tumorigenesis are linked to immunological responses, which are instrumental in immunosurveillance of cancer. However, interestingly, cancer cells circumvent such immunosurveillance through development of poorly immunogenic tumor cell variants (immunoselection) and through subversion of the immunological nanomachinery (immunosubversion). Detailed mechanistic insights of molecular specificities that regulate natural killer (NK) cell function suggest that it might be promising to design NK cell-based immunotherapeutic interventions against prostate cancer. Here, we elucidate evidence for NK cell targeting of prostate cancer proteome and address critical questions that, in our view, need thoughtfulness for the development of successful NK cell-based therapies. This review also disproves our contemporary understanding of the versatile regulators of DNA damage repair (ATM, ATR) that trigger cell surface expression of NKG2D ligands and consequent elimination of the tumor cells by NK cells and other lymphocytes that express NK cell receptors. Substantial fraction of information has been generated that guarantees productive future for this technology as more optimized constructs, better trial designs, and improved platforms are being brought from benchtop to bedside.
authors.affiliation: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College (RLMC), Lahore, Pakistan. Ammadahmad638@yahoo.com
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.forename: Sundas
authors.initials: S
authors.lastname: Fayyaz
authors.forename: Muhammad Zahid
authors.initials: MZ
authors.lastname: Qureshi
authors.forename: Sadia
authors.initials: S
authors.lastname: Rashid
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D004249:DNA Damage / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D058851:GPI-Linked Proteins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy; D020543:Proteome / Q000276:immunology*; D034622:RNA Interference / Q000276:immunology; D055607:Receptors, Natural Killer Cell / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D058851:GPI-Linked Proteins; D000949:Histocompatibility Antigens Class II; D036341:Intercellular Signaling Peptides and Proteins; D020543:Proteome; D055607:Receptors, Natural Killer Cell; C423230:ULBP2 protein, human; D019444:Vaccines, DNA; D022223:Vaccines, Subunit