Recent developments and future challenges in immune checkpoint inhibitory cancer treatment.
OBJECTIVE
In this review, we focus on the recent findings and future challenges in cancer treatment with immune checkpoint inhibitors.


RESULTS
Major progress has been made in recent years as the first immune checkpoint inhibitors are approved by the US Food and Drug Administration for the treatment of cancer patients. Anticytotoxic T-lymphocyte-associated protein 4 and antiprogrammed death protein 1/programmed death-ligand 1 (PD-L1) monoclonal antibodies are being extensively studied in many different tumor types, often showing impressive response rates, but also a typical serious toxicity profile in the form of auto-immunity. Unfortunately, it is not yet possible to prevent or predict these immune-related adverse events. Studies on mutational load, neo-epitopes, lactate dehydrogenase, PD-L1 expression, and T-cell infiltration suggest that these markers are correlating with efficacy, but have not yet reached the status of a validated biomarker for checkpoint inhibitors. Other immune checkpoints are being investigated and new checkpoint inhibitors are on the brink of being evaluated in clinical trials.


CONCLUSIONS
The main challenge for the near future will be to predict efficacy of immune checkpoint blockade and to predict and prevent immune-related adverse events. More research should be done in order to find potential biomarkers that predict treatment response and/or toxicity; the optimal administration route, dosage, and frequency; and possible combinations of therapies that have an added or synergetic effect.
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Bas D
BD
Koster
Tanja D
TD
de Gruijl
Alfons J M
AJ
van den Eertwegh
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D004359:Drug Therapy, Combination; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D058990:Molecular Targeted Therapy / Q000009:adverse effects / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor