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3 "Sang-Yeob Kim"
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Genitourinary cancer
Clinical Outcomes of Small Cell Carcinoma of the Genitourinary Tract and the Prognostic Significance of the Tumor Immune Microenvironment
Jaewon Hyung, Hyung-Don Kim, Gi Hwan Kim, Yong Mee Cho, Yeon-Mi Ryu, Sang-Yeob Kim, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee
Cancer Res Treat. 2024;56(2):624-633.   Published online November 29, 2023
DOI: https://doi.org/10.4143/crt.2023.1076
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Small cell carcinoma of the genitourinary tract (GU SCC) is a rare disease with a poor prognosis. There are only limited treatment options due to insufficient understanding of the disease. In this study, we analyzed the clinical outcomes of patients with GU SCC and their association with the tumor immune phenotype.
Materials and Methods
Patients diagnosed with GU SCC were included. Survival outcomes according to the primary location (prostate and non-prostate) and stages (limited disease [LD] and extensive disease [ED]) were analyzed. We performed multiplex immunohistochemistry (IHC) in non-prostate SCC patients and analyzed the immune cell population.
Results
A total of 77 patients were included in this study. Their median age was 71 years, 67 patients (87.0%) were male, and 48 patients (62.3%) had non-prostate SCC. All patients with ED (n=31, 40.3%) received etoposide plus platinum (EP) as initial treatment and median overall survival (OS) was 9.7 months (95% confidence interval [CI], 7.1 to 18.6). Patients with LD (n=46, 59.7%) received EP followed by radiotherapy or surgery, and 24-months OS rate was 63.6% (95% CI, 49.9 to 81.0). The multiplex IHC analysis of 21 patients with non-prostate SCC showed that patients with a higher density of programmed death-ligand 1–expressing CD68+CD206+ M2-like macrophages had significantly worse OS outcomes with an adjusted hazards ratio of 4.17 (95% CI, 1.25 to 14.29; adjusted p=0.02).
Conclusion
Patients with GU SCC had a poor prognosis, even those with localized disease. The tumor immune phenotypes were significantly associated with survival. This finding provides new insights for treating GU SCC.
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Lung and Thoracic cancer
A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer
Eo Jin Kim, Yong-Hee Cho, Dong Ha Kim, Dae-Hyun Ko, Eun-Ju Do, Sang-Yeob Kim, Yong Man Kim, Jae Seob Jung, Yoonmi Kang, Wonjun Ji, Myeong Geun Choi, Jae Cheol Lee, Jin Kyung Rho, Chang-Min Choi
Cancer Res Treat. 2022;54(4):1005-1016.   Published online December 3, 2021
DOI: https://doi.org/10.4143/crt.2021.986
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial.
Materials and Methods
Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×109 or 4×109 cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life.
Results
Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×109 cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001).
Conclusion
Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

Citations

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  • Cell therapy in sarcoma: current landscape and future directions
    Taha Koray Sahin, Theodora Germetaki, Deniz Can Guven, Serkan Akin, Omer Dizdar, Fiona Thistlethwaite, Elizabeth A Connolly, Kok Haw Jonathan Lim
    Journal for ImmunoTherapy of Cancer.2026; 14(1): e013396.     CrossRef
  • NK cell infusion is well-tolerated and shows preliminary efficacy in patients with recurrent hepatocellular carcinoma post-liver transplantation : a phase I trial
    Fan Yang, Yihang Gong, Xiaofang Zheng, Beibei Ni, Jianxi Lu, Xiaoyan Chen, Jintao Cheng, Panlong Li, Cong Du, Yunhao Chen, Yingcai Zhang, Shuhong Yi, Guoying Wang, Qi Zhang, Yang Yang, Wenjie Chen
    Journal of Translational Medicine.2026;[Epub]     CrossRef
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    Molecular Therapy Advances.2026; 34(1): 201651.     CrossRef
  • Human natural killer cells exhibit potent antifungal activity against azole-resistant Aspergillus fumigatus and diverse filamentous fungi
    Hotaka Namie, Takahiro Takazono, Satoshi Irifune, Satoru Koga, Yuya Ito, Nana Nakada, Tatsuro Hirayama, Masataka Yoshida, Kazuaki Takeda, Shotaro Ide, Naoki Iwanaga, Masato Tashiro, Naoki Hosogaya, Noriho Sakamoto, Haruki Okamura, Yoshimasa Tanaka, Katsun
    Microbiology Spectrum.2026;[Epub]     CrossRef
  • Cellular Therapies in Solid Tumors: Are We Ready for Primetime?
    Giuseppe Maiocco, Vinicius Ernani, Michael P. Gustafson, Salman R. Punekar, Konstantinos Leventakos, Julian Molina, Yousef Zakharia, Mitesh Borad, Antonious Z. Hazim
    JCO Oncology Practice.2026;[Epub]     CrossRef
  • Treatment of Alzheimer's Disease subjects with expanded non-genetically modified autologous natural killer cells (SNK01): a phase I study
    Clemente Humberto Zúñiga, Blanca Isaura Acosta, Rufino Menchaca, Cesar A. Amescua, Sean Hong, Lucia Hui, Minchan Gil, Yong-hee Rhee, Sangwook Yoon, Minji Kim, Paul Y. Chang, Yong Man Kim, Paul Y. Song, Katia Betito
    Alzheimer's Research & Therapy.2025;[Epub]     CrossRef
  • Adopting tomorrow’s therapies today: a perspective review of adoptive cell therapy in lung cancer
    Faith Abodunrin, Daniel J Olson, Oluwatosin Emehinola, Christine M Bestvina
    Therapeutic Advances in Medical Oncology.2025;[Epub]     CrossRef
  • Preclinical investigation of anti-tumor efficacy of allogeneic natural killer cells combined with cetuximab for head and neck squamous cell carcinoma
    Chaeyeon Kim, Mina Han, Gamin Kim, Wonrak Son, Jeongah Kim, Minchan Gil, Yong-Hee Rhee, Nam Suk Sim, Chang Gon Kim, Hye Ryun Kim
    Cancer Immunology, Immunotherapy.2025;[Epub]     CrossRef
  • Harnessing Immune Rejuvenation: Advances in Overcoming T Cell Senescence and Exhaustion in Cancer Immunotherapy
    Tesfahun Dessale Admasu, John S. Yu
    Aging Cell.2025;[Epub]     CrossRef
  • Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy
    Bryan Marr, Donghyeon Jo, Mihue Jang, Seung-Hwan Lee
    Immune Network.2025;[Epub]     CrossRef
  • The updated network meta-analysis of the therapeutic efficacies of lung cancer: A systematic review and meta-analysis
    Chuan-Hsin Chang, Chih-Cheng Chien, Yue-Cune Chang
    Tzu Chi Medical Journal.2025; 37(3): 339.     CrossRef
  • Synergistic Anti-Tumor Efficacy of Modified FOLFIRINOX and NK Cell Therapy in Pancreatic Ductal Adenocarcinoma
    Hye-Seong Park, Jun Eul Hwang, Je-Jung Lee, Woo Kyun Bae
    Cancers.2025; 17(17): 2785.     CrossRef
  • Machine learning-based development of a cytotoxicity prediction model for NK cell therapy in cancers
    Jie Ma, Jingjing Yue, Yangyang Li, Yutong Li, Hongbo Dong, Fang Fang, Weihua Xiao
    Cellular Oncology.2025; 48(6): 1837.     CrossRef
  • Efficacy and safety of natural killer cell therapy for the treatment of advanced non-small cell lung cancer: A meta-analysis and systematic review
    Zhengnan Li, Xiu’e Wang, Shaoqing Chen, Ping Zhang, Xiujuan Wang, Xinye Ni, Chunlin Mou
    Immunologic Research.2025;[Epub]     CrossRef
  • Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical st
    Myeong Geun Choi, Gun Woo Son, Mi Young Choi, Jae Seob Jung, Jin Kyung Rho, Wonjun Ji, Byeong Gon Yoon, Jong-Min Jo, Yong Man Kim, Dae-Hyun Ko, Jae Cheol Lee, Chang-Min Choi
    Journal for ImmunoTherapy of Cancer.2024; 12(3): e008585.     CrossRef
  • Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells
    Jaya Lakshmi Thangaraj, Michael Coffey, Edith Lopez, Dan S. Kaufman
    Cell Stem Cell.2024; 31(9): 1327.     CrossRef
  • Strategies to enhance the therapeutic efficacy of anti-PD-1 antibody, anti-PD-L1 antibody and anti-CTLA-4 antibody in cancer therapy
    Xin Su, Jian Li, Xiao Xu, Youbao Ye, Cailiu Wang, Guanglong Pang, Wenxiu Liu, Ang Liu, Changchun Zhao, Xiangyong Hao
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • Epigenetic regulation of NKG2D ligand and the rise of NK cell-based immunotherapy for cancer treatment
    Raj Kumar, Romi Gupta
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Efficacy and safety of natural killer cell therapy in patients with solid tumors: a systematic review and meta-analysis
    Heesook Park, Gyurin Kim, Najin Kim, Sungyoen Ha, Hyeonwoo Yim
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • Next-generation immunotherapy: igniting new hope for lung cancer
    Molly S. C. Li, Andrew L. S. Chan, Kevin K. S. Mok, Landon L. Chan, Tony S. K. Mok
    Therapeutic Advances in Medical Oncology.2024;[Epub]     CrossRef
  • Engineered Cellular Therapies for the Treatment of Thoracic Cancers
    Spencer M. Erickson, Benjamin M. Manning, Akhilesh Kumar, Manish R. Patel
    Cancers.2024; 17(1): 35.     CrossRef
  • Cellular Therapy in NSCLC: Between Myth and Reality
    Martina Imbimbo, Laureline Wetterwald, Alex Friedlaender, Kaushal Parikh, Alfredo Addeo
    Current Oncology Reports.2023; 25(10): 1161.     CrossRef
  • NK cell activity and methylated HOXA9 ctDNA as prognostic biomarkers in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors
    Sara Witting Christensen Wen, Line Nederby, Rikke Fredslund Andersen, Torben Schjødt Hansen, Christa Haugaard Nyhus, Ole Hilberg, Anders Jakobsen, Torben Frøstrup Hansen
    British Journal of Cancer.2023; 129(1): 135.     CrossRef
  • Harnessing Natural Killer Cells for Lung Cancer Therapy
    Shoubao Ma, Michael A. Caligiuri, Jianhua Yu
    Cancer Research.2023; 83(20): 3327.     CrossRef
  • Natural killer cells: the next wave in cancer immunotherapy
    Xin Chen, Lei Jiang, Xuesong Liu
    Frontiers in Immunology.2022;[Epub]     CrossRef
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  • 24 Web of Science
  • 25 Crossref
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Gastrointestinal cancer
Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3- CD4+ T Cells in Biliary Tract Cancer
Hyung-Don Kim, Jwa Hoon Kim, Yeon-Mi Ryu, Danbee Kim, Sunmin Lee, Jaehoon Shin, Seung-Mo Hong, Ki-Hun Kim, Dong‐Hwan Jung, Gi‐Won Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Baek-Yeol Ryoo, Jae Ho Jeong, Kyu-pyo Kim, Sang-Yeob Kim, Changhoon Yoo
Cancer Res Treat. 2021;53(1):162-171.   Published online August 31, 2020
DOI: https://doi.org/10.4143/crt.2020.704
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated.
Materials and Methods
A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core.
Results
The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS.
Conclusion
The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

Citations

Citations to this article as recorded by  
  • Metastatic microenvironment of extrahepatic cholangiocarcinoma
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  • The Evolving Landscape of the Colorectal Cancer Vaccines: From Biological Mechanisms to Translational Therapeutics
    Sabrina Brigitta Valerie Setiono, Grace Lendawati Amelia Turalaki, Trina Ekawati Tallei
    Heca Journal of Applied Sciences.2026; 4(1): 20.     CrossRef
  • Sequential involvement of hypoxia and anti-PD-1 treatment in shaping tumor-regional CD39+CD8+ T cells highlights immunotherapy-resistant features in NSCLC
    Jiajuan Wu, Jiawei Zhai, Leilei Lv, Yaoxin Zhang, Yu Shen, Qiuxia Qu, Cheng Chen
    Journal for ImmunoTherapy of Cancer.2026; 14(6): e014940.     CrossRef
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    Yunyan Dai, Chenyang Dong, Zhiming Wang, Yunpeng Zhou, Yi Wang, Yi Hao, Pinggui Chen, Chaojie Liang, Gaopeng Li
    Frontiers in Immunology.2025;[Epub]     CrossRef
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    Frontiers in Immunology.2025;[Epub]     CrossRef
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    Veysel Toprak, İlhan Özdemir, Şamil Öztürk, Orhan Yanar, Yusuf Ziya Kizildemir, Mehmet Cudi Tuncer
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    Ricardo Cartes-Velásquez, Agustín Vera, Rodrigo Torres-Quevedo, Jorge Medrano-Díaz, Andy Pérez, Camila Muñoz, Hernán Carrillo-Bestagno, Estefanía Nova-Lamperti
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    Siqi Yang, Ruiqi Zou, Yushi Dai, Yafei Hu, Fuyu Li, Haijie Hu
    International Journal of Oncology.2023;[Epub]     CrossRef
  • Therapeutic significance of tumor microenvironment in cholangiocarcinoma: focus on tumor-infiltrating T lymphocytes
    Chaoqun Li, Lei Bie, Muhua Chen, Jieer Ying
    Exploration of Targeted Anti-tumor Therapy.2023; 4(6): 1310.     CrossRef
  • Dynamic increase of M2 macrophages is associated with disease progression of colorectal cancers following cetuximab-based treatment
    Hyung-Don Kim, Sun Young Kim, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Buhm Han, Eunyoung Tak, Yeon-Mi Ryu, Sang-Yeob Kim, Tae Won Kim
    Scientific Reports.2022;[Epub]     CrossRef
  • Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma
    Taek Chung, Young Nyun Park
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
    Dong Liu, Lara Rosaline Heij, Zoltan Czigany, Edgar Dahl, Sven Arke Lang, Tom Florian Ulmer, Tom Luedde, Ulf Peter Neumann, Jan Bednarsch
    Journal of Experimental & Clinical Cancer Research.2022;[Epub]     CrossRef
  • Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
    Jwa Hoon Kim, Gi Hwan Kim, Yeon-Mi Ryu, Sang-Yeob Kim, Hyung-Don Kim, Shin Kyo Yoon, Yong Mee Cho, Jae Lyun Lee
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response
    Tong Fu, Lei-Jie Dai, Song-Yang Wu, Yi Xiao, Ding Ma, Yi-Zhou Jiang, Zhi-Ming Shao
    Journal of Hematology & Oncology.2021;[Epub]     CrossRef
  • 11,040 View
  • 245 Download
  • 21 Web of Science
  • 21 Crossref
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