Article
Immunology
Minna Sivonen, Katja A. Sirvio, Sara Wojciechowski, Anssi Kailaanmaki, Satu Kaipainen, Aubrey Bailey, Martin Villalba, Tuija Kekarainen
Summary: In this study, we aimed to identify the optimal activation and expansion protocol for cytotoxic NK cells against glioblastoma in vitro. The results showed that the ex vivo proliferation capacity and functionality of NK cells were affected by multiple factors, including the donor, composition of starting material, cytokine combination, and the activation protocol. These findings could be utilized for upscaling clinical NK cell manufacturing.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jiao Wang, Sandra Toregrosa-Allen, Bennett D. Elzey, Sagar Utturkar, Nadia Atallah Lanman, Victor Bernal-Crespo, Matthew M. Behymer, Gregory T. Knipp, Yeonhee Yun, Michael C. Veronesi, Anthony L. Sinn, Karen E. Pollok, Randy R. Brutkiewicz, Kathryn S. Nevel, Sandro Matosevic
Summary: This study demonstrates a promising strategy utilizing genetically engineered human NK cells as a multifunctional immunotherapy to target multiple mechanisms of GBM progression simultaneously, including addressing antigen escape, immunometabolic reprogramming, and immune cell homing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell & Tissue Engineering
Chloe Choi, David K. Finlay
Summary: Immunotherapy has revolutionized cancer treatment, with a focus on NK cell metabolism for improved efficacy within the tumor microenvironment.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Physiology
Priti Gupta, Charles F. Hodgman, Claudia Alvarez-Florez, Keri L. Schadler, Melissa M. Markofski, Daniel P. O'Connor, Emily C. LaVoy
Summary: This study compared the effects of three different exercise interventions on pancreatic tumor growth in mice with and without chemotherapy. The results showed that exercise interventions did not further reduce tumor growth when combined with chemotherapy. However, there was a trend for reduced tumor growth in mice not receiving chemotherapy.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Oncology
Stefania Mantovani, Stefania Varchetta, Dalila Mele, Roberta Maiello, Matteo Donadon, Cristiana Soldani, Barbara Franceschini, Guido Torzilli, Giuseppe Tartaglia, Marcello Maestri, Gaetano Piccolo, Matteo Barabino, Enrico Opocher, Stefano Bernuzzi, Mario U. Mondelli, Barbara Oliviero
Summary: This study focuses on the role of the DNAM-1/CD155 axis in mediating the NK cell response in HCC. Evidence of alterations in the axis leading to impaired NK cell cytotoxic function is provided, suggesting a potential mechanism for tumor escape and a target for new immunotherapeutic approaches.
Article
Engineering, Biomedical
Joshua D. Greenlee, Zhenjiang Zhang, Tejas Subramanian, Kevin Liu, Michael R. King
Summary: The study describes the development of liposomes that target NK cells and carry TRAIL to kill cancer cells. These liposomes are able to effectively kill resistant cancer cells and show improved efficacy under physiological conditions.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
(2023)
Article
Biochemistry & Molecular Biology
Lucas Henrique Rodrigues da Silva, Luana Correia Croda Catharino, Viviane Jennifer da Silva, Gabriela Coeli Menezes Evangelista, Jose Alexandre Marzagao Barbuto
Summary: Natural killer (NK) cells are innate lymphocytes that play a vital role in immune surveillance against tumors. Various NK-based therapies, including transfer of expanded and activated cells, genetic engineering, cytokine therapy, and tumor-specific antibody-guided cells, are being used in cancer treatment. This article also discusses the potential approaches to control glioblastoma.
Article
Immunology
Jaya Lakshmi Thangaraj, Seo-Yeon Ahn, Sung-Hoon Jung, Manh-Cuong Vo, Tan-Huy Chu, Minh-Trang Thi Phan, Minsuk Kwon, Kyung-Hwa Lee, Mihee Kim, Ga-Young Song, Deok-Hwan Yang, Jae-Sook Ahn, Hyeoung-Joon Kim, Duck Cho, Je-Jung Lee
Summary: The study shows that Dvd treatment enhances the cytotoxicity of NK cells, prolongs mouse survival, and reduces tumor burden. Furthermore, Dvd pretreatment increases NK cell persistence and homing to MM sites.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tanmoy Saha, Amanda A. van Vliet, Chunxiao Cui, Jorge Jimenez Macias, Arpita Kulkarni, Luu Nhat Pham, Sean Lawler, Jan Spanholtz, Anna-Maria Georgoudaki, Adil Doganay Duru, Aaron Goldman
Summary: Allogeneic natural killer (aNK) cell adoptive therapy has the potential to impact clinical outcomes of glioblastoma multiforme (GBM). This study introduces a BBB-permissive supramolecular cationic drug vehicle containing a heat shock protein 90 (Hsp90) inhibitor that enhances GBM cell cytotoxicity and boosts the expression of MICA/B and ULBPs, thus improving the response to clinical-grade aNK cells.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Oncology
Mohammad A. Al-Mterin, Khaled Murshed, Eyad Elkord
Summary: This study reveals that higher frequencies of tumor-infiltrating PD-1(+) NK and NKT cells are associated with longer disease-free survival (DFS) in CRC patients, while higher frequencies of tumor-infiltrating PD-1(-) NK and NKT cells are associated with shorter DFS. There are no significant associations between tumor-infiltrating PD-1(+)TIM-3(+), PD-1(+)TIGIT(+), PD-1(+)ICOS(+), PD-1(+)LAG-3(+) NK cells, and PD-1(+)TIM-3(+), PD-1(+)TIGIT(+), and PD-1(+)LAG-3(+) NKT cells with DFS.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Takahiro Miyazaki, Mekhala Maiti, Marlene Hennessy, Thomas Chang, Peiwen Kuo, Murali Addepalli, Palakshi Obalapur, Sara Sheibani, Joanna Wilczek, Rhoneil Pena, Phi Quach, Janet Cetz, Andrew Moffett, Yinyan Tang, Peter Kirk, Jicai Huang, Dawei Sheng, Ping Zhang, Werner Rubas, Loui Madakamutil, Saul Kivimae, Jonathan Zalevsky
Summary: NKTR-255, a novel polyethylene glycol-conjugate of rhIL-15, displayed similar in vitro properties to rhIL-15 but differed from precomplexed cytokines. NKTR-255 showed enhanced PK properties with prolonged IL-15R engagement, resulting in sustained proliferation and activation of NK and CD8(+) T cells. Furthermore, NKTR-255 demonstrated superior antitumor activity in a B-cell lymphoma model compared to precomplexed cytokines.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Tsutomu Nakazawa, Takayuki Morimoto, Ryosuke Maeoka, Ryosuke Matsuda, Mitsutoshi Nakamura, Fumihiko Nishimura, Noriko Ouji, Shuichi Yamada, Ichiro Nakagawa, Young Soo Park, Toshihiro Ito, Hiroyuki Nakase, Takahiro Tsujimura
Summary: This study successfully induced CIS-deleted NK cells using CRISPR/Cas9, and found that CIS deletion enhanced the anti-tumor effects of NK cells against glioblastoma. It suggests that CIS deletion could be a promising immunotherapeutic alternative for GBM patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Immunology
Thi-Anh-Thuy Tran, Young-Hee Kim, Thi-Hoang-Oanh Duong, JayaLakshmi Thangaraj, Tan-Huy Chu, Shin Jung, In-Young Kim, Kyung-Sub Moon, Young-Jin Kim, Tae-Kyu Lee, Chul Won Lee, Hyosuk Yun, Je-Jung Lee, Hyun-Ju Lee, Kyung-Hwa Lee, Tae-Young Jung
Summary: In this study, the potential therapeutic effect of natural killer (NK) cells combined with bevacizumab (Bev) and irinotecan (Iri) against glioblastoma multiforme (GBM) was investigated. It was found that Iri affected the proliferation and NK ligand expression of GBM cells, while Bev did not cause differences in these cellular processes. However, Bev modulated Iri efficacy in the intracranial (i.c) U87 mouse model.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Qi Xiong, Jiao Zhu, Yong Zhang, Hongxin Deng
Summary: Glioblastoma is the most common and deadly malignant tumor in the central nervous system. Conventional treatments like surgery, radiotherapy, and chemotherapy have limited success with high recurrence rate and poor prognosis. CAR-T cell therapy has achieved significant success in blood cancers, but its application in solid tumors like glioblastoma still faces challenges. CAR-NK cell therapy, an alternative adoptive cell therapy, shows similar anti-tumor effects and has the potential to overcome some of the limitations of CAR-T cell therapy. This article provides an overview of the preclinical research on CAR-NK cells in glioblastoma and discusses the problems and challenges in its application.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Juha P. Vayrynen, Koichiro Haruki, Mai Chan Lau, Sara A. Vayrynen, Tomotaka Ugai, Naohiko Akimoto, Rong Zhong, Melissa Zhao, Andressa Dias Costa, Jennifer Borowsky, Phoenix Bell, Yasutoshi Takashima, Kenji Fujiyoshi, Kota Arima, Junko Kishikawa, Shan-shan Shi, Tyler S. Twombly, Mingyang Song, Kana Wu, Andrew T. Chan, Xuehong Zhang, Charles S. Fuchs, Jeffrey A. Meyerhardt, Marios Giannakis, Shuji Ogino, Jonathan A. Nowak
Summary: This study developed a multiplexed immunofluorescence assay coupled with digital image analysis and machine learning to identify different lymphocytic populations in colorectal cancer. The study found that T cells were more abundant than NK and NKT-like cells in colorectal cancer. NK cells expressed high levels of a cytotoxic marker and were located closer to tumor cells, while T and NKT-like cells expressing the marker were enriched in cells closer to tumor cells. Higher densities of T and NKT-like cells were associated with longer cancer-specific survival, as well as higher densities of GZMB(+) and FCGR3A(+) NK cells and closer proximity of T and NKT-like cells to tumor cells.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Cell Biology
Tamara T. Lah, Metka Novak, Milagros A. Pena Almidon, Oliviero Marinelli, Barbara Zvar Baskovic, Bernarda Majc, Mateja Mlinar, Roman Bosnjak, Barbara Breznik, Roby Zomer, Massimo Nabissi
Summary: Among primary brain tumors, glioblastoma is the most aggressive and modern therapies have not significantly improved patient survival rates. Recent studies have shown that cannabigerol (CBG) may be a promising alternative to THC for treating glioblastoma, as it has similar anti-tumor effects without the psychoactive side effects. CBG has been found to effectively impair the progression of glioblastoma and destroy therapy-resistant cancer stem cells, suggesting it may have potential as a new adjuvant treatment strategy for this lethal cancer.
Review
Cell Biology
Bernarda Majc, Metka Novak, Natasa Kopitar-Jerala, Anahid Jewett, Barbara Breznik
Summary: Glioblastoma, the most common brain malignant tumor in adults, poses challenges for effective immunotherapy due to its intracranial location, tumor heterogeneity, and immunosuppressive microenvironment. Various promising immunotherapeutic strategies, such as vaccines, oncolytic viruses, immune checkpoint inhibitors, and adoptive cell transfer, have been applied in an attempt to promote tumor eradication and overcome immune resistance. However, discrepancies exist between preclinical studies and clinical studies in evaluating the efficiency of these strategies on glioblastoma patients.
Article
Oncology
Emanuela Senjor, Milica Perisic Nanut, Barbara Breznik, Ana Mitrovic, Jernej Mlakar, Ana Rotter, Andrej Porcnik, Tamara Lah Turnsek, Janko Kos
Summary: The study found that cystatin F expression increased with glioma progression and was mainly present in cancer stem-like cells and microglia/monocytes in tumor tissues. Internalized cystatin F affected cathepsin L activity in glioblastoma cells, reducing invasiveness and susceptibility to NK cell cytotoxicity. This suggests that cystatin F may mediate immune suppression in glioblastoma.
Article
Biochemistry & Molecular Biology
Bernarda Majc, Anamarija Habic, Metka Novak, Ana Rotter, Andrej Porcnik, Jernej Mlakar, Vera Zupunski, Ursa Pecar Fonovic, Damijan Knez, Nace Zidar, Stanislav Gobec, Janko Kos, Tamara Lah Turnsek, Anja Pislar, Barbara Breznik
Summary: This study found that cathepsin X is upregulated in human GBM tissues and localized in GBM cells, tumor-associated macrophages, and microglia. Selective cathepsin X inhibitors can decrease the viability of GBM cells and are colocalized with gamma-enolase, suggesting that cathepsin X is involved in GBM progression and could be a potential therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Cornelis J. F. van Noorden, Barbara Breznik, Metka Novak, Amber J. van Dijck, Saloua Tanan, Milos Vittori, Urban Bogataj, Noelle Bakker, Joseph D. Khoury, Remco J. Molenaar, Vashendriya V. V. Hira
Summary: Recent literature has compared energy production in cancer stem cells to their normal counterparts, revealing differences in ATP production pathways and metabolic processes. These differences are tightly regulated by cellular mechanisms, making systemic therapeutic targeting of ATP production via glycolysis or OXPHOS unattractive due to potential side effects in cancer patients.
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2022)
Article
Oncology
Alja Zottel, Metka Novak, Neja Samec, Bernarda Majc, Sara Colja, Mojca Katrasnik, Milos Vittori, Barbara Hrastar, Ana Rotter, Andrej Porcnik, Tamara Lah Turnsek, Radovan Komel, Barbara Breznik, Ivana Jovcevska
Summary: This study investigated the effect of anti-vimentin nanobody Nb79 on glioblastoma cell invasion. The results showed that vimentin is upregulated in glioblastoma tissue and Nb79 can reduce glioblastoma cell invasion. In addition, Nb79 treatment increases the expression of tight junction protein ZO-1 on the cell membrane.
Article
Oncology
Tamara T. T. Lah, Bernarda Majc, Metka Novak, Ajda Susnik, Barbara Breznik, Andrej Porcnik, Roman Bosnjak, Aleksander Sadikov, Marta Malavolta, Selma Halilcevic, Jernej Mlakar, Roby Zomer
Summary: In glioblastoma, the upregulation of GPR55 and TRPV1 receptors is correlated with GBM stem cell gene markers, making them potential targets for eliminating GBM stem cells. The mixture of CBG and CBD shows high cytotoxicity and should be further studied for its therapeutic potential in animal experiments and clinical trials.
Review
Biochemistry & Molecular Biology
Emanuela Senjor, Janko Kos, Milica Perisic Nanut
Summary: Cysteine cathepsins, the most abundant proteases in lysosomes, play essential roles in various cellular processes. Their upregulation is associated with pathological conditions such as cancer and neurodegeneration. This review provides an overview of their involvement in immune disorders and suggests potential targeting options.
Editorial Material
Genetics & Heredity
Andrea Comba, Xinzhong Li, Barbara Breznik
FRONTIERS IN GENETICS
(2023)
