Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies

Author:

Kemmotsu Naoya12,Ninomiya Kiichiro3,Kunimasa Kei4,Ishino Takamasa1,Nagasaki Joji1,Otani Yoshihiro2,Michiue Hiroyuki25,Ichihara Eiki3,Ohashi Kadoaki3,Inoue Takako4,Tamiya Motohiro4,Sakai Kazuko6,Ueda Youki1,Dansako Hiromichi1,Nishio Kazuto6,Kiura Katsuyuki3,Date Isao2,Togashi Yosuke1ORCID

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

Publisher

Wiley

Subject

Cancer Research,Oncology

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