TY - JOUR
T1 - Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies
AU - Kemmotsu, Naoya
AU - Ninomiya, Kiichiro
AU - Kunimasa, Kei
AU - Ishino, Takamasa
AU - Nagasaki, Joji
AU - Otani, Yoshihiro
AU - Michiue, Hiroyuki
AU - Ichihara, Eiki
AU - Ohashi, Kadoaki
AU - Inoue, Takako
AU - Tamiya, Motohiro
AU - Sakai, Kazuko
AU - Ueda, Youki
AU - Dansako, Hiromichi
AU - Nishio, Kazuto
AU - Kiura, Katsuyuki
AU - Date, Isao
AU - Togashi, Yosuke
N1 - Publisher Copyright:
© 2023 UICC.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Intracranial 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.
AB - Intracranial 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.
KW - cancer immunotherapy
KW - intracranial metastasis
KW - intracranial progression
KW - memory precursor effector T cell
KW - nonsmall-cell lung cancer
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U2 - 10.1002/ijc.34700
DO - 10.1002/ijc.34700
M3 - Article
C2 - 37611176
AN - SCOPUS:85168694352
SN - 0020-7136
VL - 154
SP - 169
EP - 179
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 1
ER -