Analysis of B cell repertoires and their antigen specificity in peripheral blood from cancer patients undergoing anti-PD-1 antibody therapy.
| Project/Area Number |
18K19490
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | Kanagawa Cancer Center Research Institute |
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Principal Investigator |
Sasada Tetsuro 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), がんワクチン・免疫センター, 部長 (70293967)
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| Co-Investigator(Kenkyū-buntansha) |
紅露 拓 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 技師・研究員 (90372424)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 抗PD-1抗体 / B細胞 / B細胞受容体レパトア / 抗原 / バイオマーカー / 免疫チェックポイント阻害剤 / 抗腫瘍効果 / 有害事象 / B細胞受容体 / レパトア / Ｂ細胞 / Ｂ細胞受容体 |
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| Outline of Final Research Achievements |
In this study, we have examined the clinical significance of analysis of B cell receptor (BCR) repertoires in peripheral blood from cancer patients undergoing anti-PD-1 antibody therapy. In patients with non-small cell lung cancer (n=30), the diversity of BCR repertoires was significantly reduced in those with better anti-tumor responses. In contrast, in patients with urothelial cancer (n=26), the diversity of BCR repertoires was significantly reduced in those with adverse events. Based on these results, the analysis of BCR repertoires might be clinically useful as a biomarker of immune checkpoint blockade. We are now trying to identify the antigens recognized by BCR from B cells selectively expanded in patients with better anti-tumor responses or adverse events after treatment to elucidate the mechanisms of anti-PD-1 antibody therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果から、BCRレパトア解析のバイオマーカーとしての有用性が示唆された。なお、BCRレパトア多様性の臨床的意義はがん種により異なる可能性があるため、さらに詳細な検討が望まれるが、新たな視点から免疫チェックポイント（PD-1/PD-L1）研究の展開が期待できる。本研究の成果は、抗PD-1抗体の作用メカニズムを解明するとともに、不必要な治療による不利益（有害事象合併・医療費浪費）の回避にもつながる可能性があり、臨床的意義は大きいと思われる。
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Report
(3 results)
Research Products
(41 results)
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[Journal Article] Distribution of Regulatory T-Cells and Other Phenotypes of T-Cells in Tumors and Regional Lymph Nodes of Colorectal Cancer Patients.2020
Author(s)
Kazama K, Otake J, Satoyoshi T, Shiozawa M, Sugano N, Sato S, Atsumi Y, Kano K, Murakawa M, Maezawa Y, Hashimoto I, Numata M, Oshima T, Yukawa N, Rino Y, Sasada T, Masuda M.
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Journal Title
In Vivo.
Volume: 34
Issue: 2
Pages: 849-856
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer.2020
Author(s)
Ohkuma R, Yada E, Ishikawa S, Komura D, Ishizaki H, Tamada K, Kubota Y, Hamada K, Ishida H, Hirasawa Y, Ariizumi H, Satoh E, Shida M, Watanabe M, Onoue R, Ando K, Tsurutani J, Yoshimura K, Yokobori T, Sasada T, Aoki T, Murakami M, Norose T, Ohike N, Takimoto M, Izumizaki M, Kobayashi S, Tsunoda T, Wada S.
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Journal Title
PLoS One
Volume: 10
Issue: 1
Pages: e0226707-e0226707
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Association between soluble immune mediators and tumor responses in patients with nonsmall cell lung cancer treated with anti-PD-1 inhibitor.2019
Author(s)
Matsuo N, Azuma K, Hattori S, Ohtake J, Kawahara A, Ishii H, Tokito T, Yamada K, Shibata Y, Shimokawaji T, Kondo T, Kato T, Saito H, Yamada K, Sasada T, Hoshino T.
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Journal Title
Int J Cancer.
Volume: 144
Issue: 5
Pages: 1170-1179
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma.2018
Author(s)
Narita Y, Arakawa Y, Yamasaki F, Nishikawa R, Aoki T, Kanamori M, Nagane M, Kumabe T, Hirose Y, Ichikawa T, Kobayashi H, Fujimaki T, Goto H, Takeshima H, Ueba T, Abe H, Tamiya T, Sonoda Y, Natsume A, Kakuma T, Sugita Y, Komatsu N, Yamada A, Sasada T, Matsueda S, Shichijo S, Itoh K, Terasaki M.
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Journal Title
Neuro Oncol.
Volume: 21
Issue: 3
Pages: 348-359
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] High expression of Olfactomedin-4 correlates with chemoresistance and poor prognosis for pancreatic cancer.2019
Author(s)
Ryotaro Ohkuma, Erica Yada, Yutaro Kubota, Kazuyuki Hamada, Hiroo Ishida, Yuya Hirasawa, Hirotsugu Ariizumi, Etsuko Satoh, Junji Tsurutani, Kiyoshi Yoshimura, Tetsuro Sasada, Takeshi Aoki, Masahiko Murakami, Tomoko Norose, Nobuyuki Ohike, Masafumi Takimoto, Takuya Tsunoda, Satoshi Wada.
Organizer
AACR Annual Meeting 2019
Related Report
Int'l Joint Research
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[Presentation] Early changes in plasma CXCL2 and MMP2 levels predicts the response to anti-PD-1 therapy in non-small-cell lung cancer.2019
Author(s)
Matsuo N, Azuma K, Murotani K, Ishii H, Tokito T, Yamada K,Shibata Y, Shimokawaji T, Nakahara Y, Kondo T, Kato T, Saito H, Yamada K, Sasada T, Hoshino T.
Organizer
2019 World Conference on Lung Cancer
Related Report
Int'l Joint Research
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[Presentation] Proteogenomics-based identifying neoantigens in refractory cancers using xenograft mice.2019
Author(s)
Yuko Nakamura, Susumu Iizumi, Hiroki Ueda, Shogo Yamamoto, Kenji Tatsuno, Aya Nakayama, Kazuki Yamamoto, Taku Koro, Kyoko Hasegawa, Norihiro Nakamura, Hiroyuki Aburatani, Tetsuro Sasada, Takeshi Kawamura.
Organizer
18th Human Proteome Organization World Congress
Related Report
Int'l Joint Research
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[Presentation] A novel affinity-enhanced NY-ESO-1-targeting TCR-redirected T cell transfer exhibited early-onset cytokine release syndrome and subsequent tumor responses in synovial sarcoma patients.2019
Author(s)
Hattori H, Ishihara M, Kitano S, Miyahara Y, Kato H, Mishima H, Yamamoto N, Funakoshi T, Kojima T, Sasada T, Sato E, Okamoto S, Tomura D, Chono H, Nukaya I, Mineno J, Ikeda H, Watanabe T, Kageyama S, Shiku H.
Organizer
ESMO 2019 Congress
Related Report
Int'l Joint Research
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[Presentation] Tumor responses and early onset cytokine release syndrome in synovial sarcoma patients treated with a novel affinityenhanced NY-ESO-1-targeting TCR-redirected T cell transfer.2019
Author(s)
Ishihara M, Kitano S, Hattori H, Miyahara Y, Kato H, Mishima H, Yamamoto N, Funakoshi T, Kojima T, Sasada T, Sato E, Okamoto S, Tomura D, Chono H, Nukaya I, Mineno J, Ikeda H, Watanabe T, Kageyama S, Shiku H.
Organizer
ASCO Annual Meeting 2019
Related Report
Int'l Joint Research
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[Presentation] Changes in plasma CXCL2 and MMP2 levels reflect response to anti-PD-1 therapy in non-small-cell lung cancer patients.2019
Author(s)
Norikazu Matsuo, Koichi Azuma, Kenta Murotani, Yoshiko Naito, Hidenobu Ishii, Takaaki Tokito, Tadasuke Shimokawaji, Yoshiro Nakahara, Tetsuro Kondo, Terufumi Kato Haruhiro Saito, Kouzo Yamada, Tetsuro Sasada, Tomoaki Hoshino.
Organizer
第17回日本臨床腫瘍学会学術集会
Related Report
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[Presentation] Changes of BCR repertoire are predictive biomarker for the efficacy of immune checkpoint inhibitor in NSCLC.2019
Author(s)
Yoshiro Nakahara, Norikazu Matsuo, Koichi Azuma, Yoshiko Naito, Hidenobu Ishii, Takaaki Tokito, Yuka Igarashi, Taku Kouro, Ryo Usui, Tadasuke Shimokawaji, Tetsuro Kondo, Terufumi Kato, Haruhiro Saito, Kouzo Yamada, Tomoaki Hoshino, Tetsuro Sasada.
Organizer
第17回日本臨床腫瘍学会学術集会
Related Report
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