Article
Cell Biology
Miguel Olivas-Aguirre, Laura Hadit Cruz-Aguilar, Igor Pottosin, Oxana Dobrovinskaya
Summary: This study found that the selective blocker of KCa3.1 channel NS6180 can significantly reduce store-operated calcium entry (SOCE) and intracellular calcium elevation in NK cells, thereby enhancing the killing efficiency of NK cells.
Article
Oncology
Yudai Murayama, Yasushi Kasahara, Nobuhiro Kubo, Chansu Shin, Masaru Imamura, Naoki Oike, Takashi Ariizumi, Akihiko Saitoh, Minori Baba, Tomohiro Miyazaki, Yuko Suzuki, Yiwei Ling, Shujiro Okuda, Keichiro Mihara, Akira Ogose, Hiroyuki Kawashima, Chihaya Imai
Summary: The study found that ligands for NKp44 and NKp30 were expressed in all cell lines, while NKG2D ligands were only minimally expressed in one cell line. Primary synovial sarcoma cells expressed the mRNA of the truncated isoform of MLL5, a known cellular ligand for NKp44. NKp44-based CAR T cells specifically recognized synovial sarcoma cells and exerted suppressive effects on tumor cell growth.
TRANSLATIONAL ONCOLOGY
(2022)
Article
Immunology
Grace Lee, Robert Schauner, Juanita Burke, Jade Borocz, Smitha Vasana, Lukasz Sobieraj, Maria Giraudo, Zachary Jackson, Qasim Ansari, Maria Navas, Hany Sakr, David Wald
Summary: SARS-CoV-2 has caused a global pandemic with significant morbidity and mortality. This study identifies specific clusters of NK cells associated with COVID-19 and characterizes the phenotype of COVID-19 positive NK cells. Blocking NKG2A and KIR2DL1 receptors enhances the ability of NK cells from COVID-19 positive patients to kill SARS-CoV-2 infected cells, suggesting a potential therapeutic approach.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Seok-Min Kim, Se-Chan Oh, Sun-Young Lee, Ling-Zu Kong, Jong-Hee Lee, Tae-Don Kim
Summary: N-6-Methyladenosine (m(6)A) is an abundant epitranscriptomic mark involved in multiple mRNA metabolism processes. This study explores the role of FTO, an m(6)A eraser, in natural killer (NK) cell immunity. FTO deficiency in NK cells leads to hyperactivation and enhances antitumor response against leukemia. Mechanistically, FTO regulates IL-2/15-driven JAK/STAT signaling by stabilizing suppressor of cytokine signaling protein (SOCS) family genes. These findings highlight that FTO is a crucial modulator of NK cell immunity and provide a potential immunotherapeutic strategy for allogeneic NK cell therapies.
Article
Oncology
Nai-Shan Zheng, Xiang-Yu Zhao, Ding Wei, Jin-Lin Miao, Ze-Kun Liu, Yu-Le Yong, Ren-Yu Zhang, Yi-Xiao Guo, Lin He, Bin Wang, Xiu-Xuan Sun, Hai-Jiao Yang, Tian-Jiao Zhang, Qian He, Xiao-Min Li, Hai Zhang, Rong Hou, Peng Lin, Ying-Ming Xu, Xiao-Jun Huang, Zhi-Nan Chen, Huijie Bian
Summary: CD147-CAR T cell therapy shows potent anti-tumor activity against T cell acute lymphoblastic leukemia (T-ALL) and potential safety towards normal cells and CD147-deficient cells.
Article
Biochemistry & Molecular Biology
Estefani Garcia-Rios, Alejandra Leivas, Francisco J. Mancebo, Laura Sanchez-Vega, Diego Lanzarot, Jose Maria Aguado, Joaquin Martinez-Lopez, Maria Liz Paciello, Pilar Perez-Romero
Summary: The study demonstrates the ability to efficiently stimulate SARS-CoV-2-specific T-cells from convalescent donors and the increased percentage of these cells in vaccinated convalescent donors. These findings suggest the potential clinical usefulness of isolated SARS-CoV-2-specific T-cells.
Article
Immunology
Qiao Liu, Lisha Wang, Huayu Lin, Zhiming Wang, Jialin Wu, Junyi Guo, Shuqiong Wen, Ling Ran, Zhengliang Yue, Xingxing Su, Qing Wu, Jianfang Tang, Zhirong Li, Li Hu, Lifan Xu, Lilin Ye, Qizhao Huang
Summary: Cytotoxic CD8(+) T cells are the main focus of anti-tumor immunity and immunotherapy research, but transferred tumor-specific CD8(+) T cells have limited effect on suppressing tumor growth. On the other hand, CD4(+) T cells play an important role in curtailing tumor metastasis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna S. Smagina, Sergey Kulemzin, Gaukhar M. Yusubalieva, Anna G. Kedrova, Andrey E. Sanzharov, Yurii Ivanov, Darya A. Matvienko, Vladimir A. Kalsin, Andrey A. Gorchakov, Vladimir P. Baklaushev, Aleksandr Taranin
Summary: Immunotherapy with genetically engineered T- and NK-cells has shown high efficacy in certain B-cell malignancies, with NK cells as carriers of CARs showing promise for reducing treatment costs and reaching more patients. Derivative YT-VAV1 cells with enhanced cytotoxicity outperform parental YT cells in vitro.
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Yuqing Zhang, Huocong Huang, Morgan Coleman, Arturas Ziemys, Purva Gopal, Syed M. Kazmi, Rolf A. Brekken
Summary: Studies have shown that VEGF induces an immunosuppressive phenotype in VEGFR2* myeloid cells, while VEGF blockade inhibits this phenotype and enhances T cell activation, improving the efficacy of immune checkpoint blockade. This indicates the potential of VEGF inhibition in potentiating immune therapy for cancer.
Article
Oncology
Elisaveta Voynova, Nga Hawk, Francis A. Flomerfelt, William G. Telford, Ronald E. Gress, Jennifer A. Kanakry, Damian Kovalovsky
Summary: Chimeric antigen receptors (CAR) can redirect the activity of NK cells to target T-cell malignancies. Recognition of CD5 molecules in malignant T cells by the CAR leads to improved antitumor response compared to targeting CD3. A specific CAR-NK framework has superior activity on NK effector cells. CD3-CAR-T is more active than CD5-CAR-T in vitro, but less efficient in eliminating tumor cells in vivo. The CAR-NK framework greatly improves the efficacy of CARs in NK cells.
Article
Virology
Hanyu Pan, Xinyi Yang, Jing Wang, Huitong Liang, Zhengtao Jiang, Lin Zhao, Yanan Wang, Zhiming Liang, Xiaoting Shen, Qinru Lin, Yue Liang, Jinglong Yang, Panpan Lu, Yuqi Zhu, Min Li, Pengfei Wang, Jianqing Xu, Hongzhou Lu, Huanzhang Zhu
Summary: HIV-specific CAR-T cells have been developed to target HIV-1 infected CD4+ T-cells expressing HIV Env proteins. The use of a 3BE CAR construct allowed for the expression of a PD-1 blocking scFv and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117. These CAR-T cells showed enhanced cytotoxic activity, proliferation capability, killing efficiency, and cytokine secretion against HIV Env+ cells compared to T cells expressing 3BNC117-CAR alone. TCR-deficient 3BE CAR-T cells effectively killed HIV Env+ cells in vivo without causing severe graft-versus-host disease in mice. This approach could be a powerful therapeutic candidate for the functional cure of HIV.
Editorial Material
Medicine, General & Internal
Elizabeth G. Phimister, Eric J. Rubin
Summary: This article explains the components and concepts of a study on therapeutic targeting of pancreatic cancer using engineered autologous T cells with specific targeting ability for cancer cells.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Immunology
Emily R. Kansler, Saida Dadi, Chirag Krishna, Briana G. Nixon, Efstathios G. Stamatiades, Ming Liu, Fengshen Kuo, Jing Zhang, Xian Zhang, Kristelle Capistrano, Kyle A. Blum, Kate Weiss, Ross M. Kedl, Guangwei Cui, Koichi Ikuta, Timothy A. Chan, Christina S. Leslie, A. Ari Hakimi, Ming O. Li
Summary: This study reveals an innate immune surveillance response mediated by cytotoxic ILC1 sensing of cancer cell-expressed IL-15, which is associated with patient survival and contributes to tumor suppression.
Article
Biochemistry & Molecular Biology
Jesper van Eck van der Sluijs, Diede van Ens, Jolanda Brummelman, Daan Heister, Aastha Sareen, Lisa Truijen, Dorette S. van Ingen Schenau, Mirjam H. M. Heemskerk, Marieke Griffioen, Michel G. D. Kester, Nicolaas P. M. Schaap, Joop H. Jansen, Anniek B. van der Waart, Harry Dolstra, Willemijn Hobo
Summary: Non-DCs have been found to enhance the activation and expansion of antigen-specific CD8+ T cells mediated by DCs, without impairing the NK cell responses in vitro and in vivo. This provides a rationale for further clinical translation of the CD34+-derived DC-complete vaccine in hemato-oncology patients post alloSCT.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Roxana Khazen, Marine Cazaux, Fabrice Lemaitre, Beatrice Corre, Zacarias Garcia, Philippe Bousso
Summary: The majority of CTL interactions with tumor cells either in vitro or in vivo result in sublethal hits, which are associated with reversible calcium elevation and membrane damage in the target cells. In the therapeutic context of anti-CD19 CAR T cells, most interactions with tumor cells do not lead to lethal hit delivery. Differences in CTL lytic potential and tumor cell resistance to cytotoxic hits are two important barriers for effective anti-tumor responses in vivo.