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.

Melaiu, O., Lucarini, V., Giovannoni, R., Fruci, D., Gemignani, F. (2022). News on immune checkpoint inhibitors as immunotherapy strategies in adult and pediatric solid tumors. SEMINARS IN CANCER BIOLOGY, 79, 18-43 [10.1016/j.semcancer.2020.07.001].

News on immune checkpoint inhibitors as immunotherapy strategies in adult and pediatric solid tumors

Melaiu O.;
2022

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.
Pubblicato
Rilevanza internazionale
Recensione
Esperti anonimi
Settore MED/05
English
Adult cancers
Clinical trials
Immune checkpoint inhibitors
Immunotherapy
Pediatric cancers
Adolescent
Antineoplastic Combined Chemotherapy Protocols
B7 Antigens
B7-H1 Antigen
Biomarkers, Tumor
CTLA-4 Antigen
Child
Child, Preschool
Combined Modality Therapy
Humans
Immune Checkpoint Inhibitors
Immunologic Factors
Immunotherapy
Infant
Infant, Newborn
Neoplasms
Programmed Cell Death 1 Receptor
Treatment Outcome
Melaiu, O., Lucarini, V., Giovannoni, R., Fruci, D., Gemignani, F. (2022). News on immune checkpoint inhibitors as immunotherapy strategies in adult and pediatric solid tumors. SEMINARS IN CANCER BIOLOGY, 79, 18-43 [10.1016/j.semcancer.2020.07.001].
Melaiu, O; Lucarini, V; Giovannoni, R; Fruci, D; Gemignani, F
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/305962
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