Circulating tumor-associated antigen-specific IFNγ+4-1BB+ CD8+ T cells as peripheral biomarkers of treatment outcomes in patients with pancreatic cancer

被引:0
作者
Murakami, Hirotomo [1 ,2 ]
Takahama, Shokichi [1 ]
Akita, Hirofumi [1 ,3 ,4 ]
Kobayashi, Shogo [2 ]
Masuta, Yuji [1 ]
Nagatsuka, Yuta [1 ,2 ]
Higashiguchi, Masaya [1 ,2 ]
Tomokuni, Akira [5 ]
Yoshida, Keiichi [4 ]
Takahashi, Hidenori [2 ]
Doki, Yuichiro [2 ]
Eguchi, Hidetoshi [2 ]
Matsuura, Nariaki [3 ]
Yamamoto, Takuya [1 ,4 ,6 ,7 ]
机构
[1] Natl Inst Biomed Innovat Hlth & Nutr, Ctr Intractable Dis & ImmunoGen, Lab Precis Immunol, Osaka, Japan
[2] Osaka Univ, Grad Sch Med, Dept Gastroenterol Surg, Osaka, Japan
[3] Osaka Int Canc Inst, Dept Gastroenterol Surg, Osaka, Japan
[4] Osaka Int Canc Inst, Next Generat Precis Med Res Ctr, Osaka, Japan
[5] Osaka Gen Med Ctr, Dept Gastroenterol Surg, Osaka, Japan
[6] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Aging & Immune Regulat, Osaka, Japan
[7] Osaka Univ, Grad Sch Med, Dept Biomed Informat, Osaka, Japan
基金
日本学术振兴会;
关键词
pancreatic cancer; tumor-associated antigen-specific CD8( + )T cells; PBMC; prognostic marker; immune checkpoint inhibition; CHEMOTHERAPY; PEMBROLIZUMAB; BLOCKADE; ADJUVANT; IMMUNITY; PEPTIDE;
D O I
10.3389/fimmu.2024.1363568
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD8(+) T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8(+) T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFN gamma(+)4-1BB(+) CD8(+) T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFN gamma(+)4-1BB(+) CD8(+) T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFN gamma(+)4-1BB(+) CD8(+) T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8(+) T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy.
引用
收藏
页数:12
相关论文
共 51 条
[21]   OMIP-009: Characterization of antigen-specific human T-cells [J].
Lamoreaux, Laurie ;
Koup, Richard A. ;
Roederer, Mario .
CYTOMETRY PART A, 2012, 81A (05) :362-363
[22]   Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA [J].
Lee, Jee-Soo ;
Park, Sung Sup ;
Lee, Young Kyung ;
Norton, Jeffrey A. ;
Jeffrey, Stefanie S. .
MOLECULAR ONCOLOGY, 2019, 13 (08) :1623-1650
[23]   The landscape of cancer cell line metabolism [J].
Li, Haoxin ;
Ning, Shaoyang ;
Ghandi, Mahmoud ;
Kryukov, Gregory V. ;
Gopal, Shuba ;
Deik, Amy ;
Souza, Amanda ;
Pierce, Kerry ;
Keskula, Paula ;
Hernandez, Desiree ;
Ann, Julie ;
Shkoza, Dojna ;
Apfel, Verena ;
Zou, Yilong ;
Vazquez, Francisca ;
Barretina, Jordi ;
Pagliarini, Raymond A. ;
Galli, Giorgio G. ;
Root, David E. ;
Hahn, William C. ;
Tsherniak, Aviad ;
Giannakis, Marios ;
Schreiber, Stuart L. ;
Clish, Clary B. ;
Garraway, Levi A. ;
Sellers, William R. .
NATURE MEDICINE, 2019, 25 (05) :850-+
[24]   Timing of neoadjuvant immunotherapy in relation to surgery is crucial for outcome [J].
Lio, Jing ;
O'Donnell, Jake S. ;
Yan, Juming ;
Madore, Jason ;
Allen, Stacey ;
Smyth, Mark J. ;
Teng, Michele W. L. .
ONCOIMMUNOLOGY, 2019, 8 (05)
[25]   Sequencing Ipilimumab Immunotherapy Before or After Chemotherapy (Nab-Paclitaxel and Bevacizumab) for the Treatment of BRAFwt (BRAF Wild-Type) Metastatic Malignant Melanoma Results of a Study of Academic and Community Cancer Research United (ACCRU) RU261206I [J].
Markovic, Svetomir N. ;
Suman, Vera J. ;
Javed, Asad ;
Reid, Joel M. ;
Wall, Darci J. ;
Erickson, Lori A. ;
Ernstoff, Marc ;
Anderson, Daniel M. .
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2020, 43 (02) :115-121
[26]   The evolving translational potential of small extracellular vesicles in cancer [J].
Moller, Andreas ;
Lobb, Richard J. .
NATURE REVIEWS CANCER, 2020, 20 (12) :697-709
[27]   Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma [J].
Motzer, R. J. ;
Escudier, B. ;
McDermott, D. F. ;
George, S. ;
Hammers, H. J. ;
Srinivas, S. ;
Tykodi, S. S. ;
Sosman, J. A. ;
Procopio, G. ;
Plimack, E. R. ;
Castellano, D. ;
Choueiri, T. K. ;
Gurney, H. ;
Donskov, F. ;
Bono, P. ;
Wagstaff, J. ;
Gauler, T. C. ;
Ueda, T. ;
Tomita, Y. ;
Schutz, F. A. ;
Kollmannsberger, C. ;
Larkin, J. ;
Ravaud, A. ;
Simon, J. S. ;
Xu, L-A ;
Waxman, I. M. ;
Sharma, P. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (19) :1803-1813
[28]   Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial [J].
Neoptolemos, John P. ;
Palmer, Daniel H. ;
Ghaneh, Paula ;
Psarelli, Eftychia E. ;
Valle, Juan W. ;
Halloran, Christopher M. ;
Faluyi, Olusola ;
O'Reilly, Derek A. ;
Cunningham, David ;
Wadsley, Jonathan ;
Darby, Suzanne ;
Meyer, Tim ;
Gillmore, Roopinder ;
Anthoney, Alan ;
Lind, Pehr ;
Glimelius, Bengt ;
Falk, Stephen ;
Izbicki, Jakob R. ;
Middleton, Gary William ;
Cummins, Sebastian ;
Ross, Paul J. ;
Wasan, Harpreet ;
McDonald, Alec ;
Crosby, Tom ;
Ma, Yuk Ting ;
Patel, Kinnari ;
Sherriff, David ;
Soomal, Rubin ;
Borg, David ;
Sothi, Sharmila ;
Hammel, Pascal ;
Hackert, Thilo ;
Jackson, Richard ;
Buechler, Markus W. .
LANCET, 2017, 389 (10073) :1011-1024
[29]   Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study [J].
Nishida, Sumiyuki ;
Ishikawa, Takeshi ;
Egawa, Shinichi ;
Koido, Shigeo ;
Yanagimoto, Hiroaki ;
Ishii, Jun ;
Kanno, Yoshihide ;
Kokura, Satoshi ;
Yasuda, Hiroaki ;
Oba, Mari Saito ;
Sato, Maho ;
Morimoto, Soyoko ;
Fujiki, Fumihiro ;
Eguchi, Hidetoshi ;
Nagano, Hiroaki ;
Kumanogoh, Atsushi ;
Unno, Michiaki ;
Kon, Masanori ;
Shimada, Hideaki ;
Ito, Kei ;
Homma, Sadamu ;
Oka, Yoshihiro ;
Morita, Satoshi ;
Sugiyama, Haruo .
CANCER IMMUNOLOGY RESEARCH, 2018, 6 (03) :320-331
[30]   The Promise of Neoadjuvant Immunotherapy and Surgery for Cancer Treatment [J].
O'Donnell, Jake S. ;
Hoefsmit, Esmee P. ;
Smyth, Mark J. ;
Blank, Christian U. ;
Teng, Michele W. L. .
CLINICAL CANCER RESEARCH, 2019, 25 (19) :5743-5751