Affiliation:
1. Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Okayama Japan
2. Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Okayama Japan
3. Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Okayama Japan
4. Department of Thoracic Oncology Osaka International Cancer Institute Osaka Japan
5. Neutron Therapy Research Center Okayama University Okayama Japan
6. Department of Genome Biology Kindai University Faculty of Medicine Osaka‐Sayama Japan
Abstract
AbstractIntracranial metastases are common in nonsmall‐cell lung cancer (NSCLC) patients, whose prognosis is very poor. In addition, intracranial progression is common during systemic treatments due to the inability to penetrate central nervous system (CNS) barriers, whereas the intracranial effects of cancer immunotherapies remain unclear. We analyzed clinical data to evaluate the frequency of intracranial progression in advanced NSCLC patients treated with PD‐1 blockade therapies compared with those treated without PD‐1 blockade therapies, and found that the frequency of intracranial progression in advanced NSCLC patients treated with PD‐1 blockade therapies was significantly lower than that in patients treated with cytotoxic chemotherapies. In murine models, intracranial rechallenged tumors after initial rejection by PD‐1 blockade were suppressed. Accordingly, long‐lived memory precursor effector T cells and antigen‐specific T cells were increased by PD‐1 blockade in intracranial lesions. However, intracranial rechallenged different tumors are not suppressed. Our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long‐term effects intracranially as well as systemically. If intracranial recurrence occurs during the treatment with PD‐1 blockade therapies, aggressive local therapies could be worthwhile.
Funder
Astellas Foundation for Research on Metabolic Disorders
Inamori Foundation
Japan Agency for Medical Research and Development
Japan Science and Technology Agency
Japan Society for the Promotion of Science
Kato Memorial Bioscience Foundation
MSD Life Science Foundation, Public Interest Incorporated Foundation
Naito Foundation
Ono Medical Research Foundation
Princess Takamatsu Cancer Research Fund
Suzuken Memorial Foundation
Takeda Science Foundation
Ube Foundation