News on immune checkpoint inhibitors as immunotherapy strategies in adult and pediatric solid tumors. (February 2022)

• Record Type: Journal Article
• Authors: Melaiu, Ombretta; Lucarini, Valeria; Giovannoni, Roberto; Fruci, Doriana; Gemignani, Federica
• Is Part Of: Seminars in cancer biology. Volume 79(2022)
• Page Start: 18
• Page End: 43
• Publication Date: 2022-02
• Subjects: ACT Adoptive cell therapy -- AST Advanced Solid Tumors -- ASPS Alveolar Soft Part Sarcoma -- ADT Androgen deprivation therapy -- APC Antigen-presenting cells -- AD Autoimmune diseases -- BTLA B- and T-lymphocyte attenuator -- bMMRD Biallelic mismatch repair deficiency -- BTC Biliary Tract carcinoma -- BlC Bladder carcinoma -- BM Bone marrow -- BC Breast cancer -- Ceacam-1 Carcinoembryonic Antigen Related Cell Adhesion Molecule 1 -- CNS Central nervous system -- CeC Cervical Cancer -- CST Childhood Solid Tumors -- COAD Colon adenocarcinoma -- CC Colon cancer -- CRC Colorectal cancer -- CTLA-4 Cytotoxic T-lymphocyte antigen 4 -- DC Dendritic cell -- DSRCT Desmoplastic Small Round Cell Tumor -- DIPG Diffuse intrinsic pontine glioma -- DFS Disease free survival -- EnC Endometrial Cancer -- PE Ependymoma -- MHC Peptide-major histocompatibility complexes -- EC Esophageal cancer -- EWS Ewing's sarcoma -- Gal-9 Galectin-9 -- GC Gastric cancer -- GBM Glioblastoma multiforme -- GD Grave's disease -- HB Hepatoblastoma -- HCC Hepatocellular carcinoma -- HVEM Herpes virus entry mediator -- HMGB1 High-mobility group protein B1 -- IC immune checkpoint -- ICIs Immune checkpoint inhibitors -- Ig Immunoglobulin -- IHC Immunohistochemistry -- ITIM Immunoreceptor tyrosine-based inhibitory motif -- IDO-1 Indoleamine 2, 3-dioxygenase -- LC Lung cancer -- LAG-3 Lymphocyte activation gene 3 -- MM Malignant Melanoma -- MB Medulloblastoma -- MCC Merkel cell carcinoma -- MPM Malignant pleural mesothelioma -- mlBG Metaiodobenzylguanidine -- MSI Microsatellite instability -- MDSC Myeloid-derived suppressor cells -- NC Nasopharyngeal Carcinoma -- NK Natural killer -- NB Neuroblastoma -- NSCLC Non–small-cell lung cancer -- OrC Oropharyngeal Carcinoma -- OSS Osteosarcoma -- OC Ovarian cancer -- OS Overall survival -- PC Pancreatic cancer -- PtdSer Phospatidyl serine -- PD-1 Programmed cell Death 1 -- PrC Prostate cancer -- Treg cells Regulatory T cells -- RCC Renal cell carcinoma -- RMS Rhabdomyosarcoma -- RA Rheumatoid arthritis -- SCLC Small cell lung cancer -- STS Soft tissue sarcoma -- SCC Squamous Cell Carcinoma -- SCCHN Squamous cell carcinoma of the head and neck -- TIGIT T-cell Ig and ITIM domain -- TIM-3 T-cell Ig and mucin domain 3 -- TCR T-cell receptor -- TNBC Triple negative breast cancer -- TILs Tumor infiltrating lymphocytes -- TME Tumor microenvironment -- Th1 Type 1 CD4 helper -- UC Urothelial carcinoma -- WT Wilm's tumor; Adult cancers -- Pediatric cancers -- Immune checkpoint inhibitors -- Clinical trials -- Immunotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2020.07.001
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Immune checkpoint inhibitors (ICIs) have shown unprecedented benefits in various adult cancers, and this success has prompted the exploration of ICI therapy even in childhood malignances. Although the use of ICIs as individual agents has achieved disappointing response rates, combinational therapies are likely to promise better results. However, only a subset of patients experienced prolonged clinical effects, thus suggesting the need to identify robust bio-markers that predict individual clinical response or resistance to ICI therapy as the main challenge. In this review, we focus on how the use of ICIs in adult cancers can be translated into pediatric malignances. We discuss the physiological mechanism of action of each IC, including PD-1, PD-L1 and CTLA-4 and the new emerging ones, LAG-3, TIM-3, TIGIT, B7-H3, BTLA and IDO-1, and evaluate their prognostic value in both adult and childhood tumors. Furthermore, we offer an overview of preclinical models and clinical trials currently under investigation to improve the effectiveness of cancer immunotherapies in these patients. Finally, we outline the main predictive factors that influence the efficacy of ICIs, in order to lay the basis for the development of a pan-cancer immunogenomic model, able to direct young patients towards more specific immunotherapy.