Review
Immunology
Karthik Dhatchinamoorthy, Jeff D. Colbert, Kenneth L. Rock
Summary: Loss of MHC I antigen presentation is common in many cancers, which may impair immune responses and affect the efficacy of immunotherapy. Studies have discussed underlying mechanisms through which some cancers evade immune killing by shutting down the MHC I pathway, and proposed potential strategies to overcome this limitation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Patricia T. Illing, Andy van Hateren, Rachel Darley, Nathan P. Croft, Nicole A. Mifsud, Samuel King, Lyudmila Kostenko, Mandvi Bharadwaj, James McCluskey, Tim Elliott, Anthony W. Purcell
Summary: Abacavir hypersensitivity syndrome occurs in individuals with a specific gene expression, altering immune responses. Research shows that abacavir affects the assembly of HLA-B*57:01 complexes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Kathryn Hussey, Alison Caldwell, Alexandre Kreiss, Karsten Skjodt, Annalisa Gastaldello, Ruth Pye, Rodrigo Hamede, Gregory M. Woods, Hannah Siddle
Summary: Devil facial tumour disease (DFTD) is a transmissible cancer in Tasmanian devils. It evades the host immune response by reducing major histocompatibility complex class I (MHC-I) expression, but the absence of MHC-I should activate natural killer (NK) cells. The study also found the expression of nonclassical MHC-I Saha-UD in DFTD tumors, which may serve as an immunosuppressive mechanism.
Article
Multidisciplinary Sciences
Yiwen Zhang, Yingshi Chen, Yuzhuang Li, Feng Huang, Baohong Luo, Yaochang Yuan, Baijin Xia, Xiancai Ma, Tao Yang, Fei Yu, Jun Liu, Bingfeng Liu, Zheng Song, Jingliang Chen, Shumei Yan, Liyang Wu, Ting Pan, Xu Zhang, Rong Li, Wenjing Huang, Xin He, Fei Xiao, Junsong Zhang, Hui Zhang
Summary: COVID-19, caused by SARS-CoV-2, significantly differs from SARS in its clinical and pathological characteristics. The viral protein ORF8 of SARS-CoV-2 interacts with MHC-I molecules, leading to their down-regulation and impairment of antigen presentation system, proposing ORF8 inhibition as a potential strategy for improving immune surveillance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Xiaoguang Wang, Brittany C. Waschke, Rachel A. Woolaver, Samantha M. Y. Chen, Zhangguo Chen, Jing H. Wang
Summary: Chemotherapy-treated cancer cells can activate CD8 T cells in an MHC class I-independent manner, leading to the generation of virtual memory (VM) CD8 T cells which may provide superior therapeutic effects on MHC class I-deficient tumors.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Oncology
Tsuyoshi Kadomatsu, Chiaki Hara, Ryoma Kurahashi, Haruki Horiguchi, Jun Morinaga, Keishi Miyata, Sohtaro Kurano, Hisashi Kanemaru, Satoshi Fukushima, Kimi Araki, Masaya Baba, W. Marston Linehan, Tomomi Kamba, Yuichi Oike
Summary: Deficiency of ANGPTL2 in renal tubular epithelial cells slows tumor progression in the tRCC mouse model and promotes infiltration of activated CD8(+) T-cells in kidney tissues. Moreover, Angptl2-deficient tumor cells show enhanced interferon gamma-induced expression of MHC-I and increased susceptibility to CD8(+) T-cell-mediated anti-tumor immune responses.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Katarina Pinjusic, Olivier Andreas Dubey, Olga Egorova, Sina Nassiri, Etienne Meylan, Julien Faget, Daniel Beat Constam
Summary: This study reveals that Activin-A secretion by melanoma cells inhibits adaptive antitumor immunity by indirectly inhibiting CD8(+) T cell infiltration, regardless of BRAF status. It is also found that Activin-A/INHBA expression is correlated with resistance to anti-PD1 therapy in melanoma patients and impairs response to combination anti-cytotoxic T-Lymphocyte associated protein 4/anti-PD1 treatment in preclinical models.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
David H. Margulies, Jiansheng Jiang, Javeed Ahmad, Lisa F. Boyd, Kannan Natarajan
Summary: Peptide loading of MHC-I molecules plays a critical role in the response of T cells to infections and tumors. Recent advances in structural methods have improved our understanding of the biophysical parameters that govern peptide selection, binding, and surface display. The current understanding of this cellular process is based on various approaches, and further studies are needed to explore its details and potential applications in immunization and therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Miyu Moriyama, Carolina Lucas, Valter Silva Monteiro, Akiko Iwasaki
Summary: Variants of concern (VOCs) of the SARS-CoV-2 virus have mutations that resist neutralizing antibodies, leading to breakthrough infections and reinfections. This study shows that VOCs also have the ability to suppress the expression of major histocompatibility complex class I (MHC-I), which is involved in T cell-mediated immunity. The Omicron subvariants exhibit even greater suppression of MHC-I expression, potentially contributing to their success in causing breakthrough infections and reinfections by evading T cell recognition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Uxia Gestal-Mato, Lina Herhaus
Summary: The major histocompatibility complex (MHC) class I presents peptide antigens to CD8+ T lymphocytes to trigger immune response. Besides the conventional antigen-processing pathway, autophagy also plays a role in MHC-I peptide loading and presentation. This review article explores the involvement of autophagy in MHC class I-restricted antigen presentation and its potential implications in T cell immunotherapies.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Jeff D. Colbert, Freidrich M. Cruz, Christina E. Baer, Kenneth L. Rock
Summary: This study reveals a molecular association between Tspan5 and MHC I molecules that is critical for the formation of MHC I nanoclusters and optimal T cell responses to antigens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Manola Moretti, Rosanna La Rocca, Michela Perrone Donnorso, Bruno Torre, Claudio Canale, Mario Malerba, Gobind Das, Rosa Sottile, Cinzia Garofalo, Adnane Achour, Klas Karre, Ennio Carbone, Enzo Di Fabrizio
Summary: The activation of T cell-mediated immune response depends on the interaction between T cell receptors and MHC molecules on antigen-presenting cells. In cancer cells, the reduced expression of MHC-I molecules and alterations in local mechanical properties may contribute to the evasion of the immune system.
Article
Chemistry, Physical
Honglin Xu, Kaiyuan Song, Lin-Tai Da
Summary: The study reveals the key intermediate states during the peptide loading process into TAPBPR-bound MHC-I and identifies the key structural factors responsible for the dynamics of peptide loading. The binding of TAPBPR at the MHC-I pocket-F reshapes the distant pocket-B through allosteric regulations, promoting the loading of the peptide. The partially loaded peptide weakens the stability of the TAPBPR-MHC interaction and affects the binding site through allosteric perturbations and direct contacts.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Immunology
Marlieke L. M. Jongsma, Antonius A. de Waard, Matthijs Raaben, Tao Zhang, Birol Cabukusta, Rene Platzer, Vincent A. Blomen, Anastasia Xagara, Tamara Verkerk, Sophie Bliss, Xiangrui Kong, Carolin Gerke, Lennert Janssen, Elmer Stickel, Stephanie Holst, Rosina Plomp, Arend Mulder, Soldano Ferrone, Frans H. J. Claas, Mirjam H. M. Heemskerk, Marieke Griffioen, Anne Halenius, Hermen Overkleeft, Johannes B. Huppa, Manfred Wuhrer, Thijn R. Brummelkamp, Jacques Neefjes, Robbert M. Spaapen
Summary: HLA class I glycoproteins play a crucial role in driving immune responses by presenting antigens, but tumors and pathogens often exploit this process for immune evasion. Through genome-wide screens, it was discovered that the cell surface glycosphingolipid repertoire determines effective HLA-I antigen presentation. Inhibition of GSL synthesis may represent a potential therapeutic target in cancer, infection, and autoimmunity, offering a promising avenue for immune modulation.
Article
Immunology
Andreas Walker, Tatjana Schwarz, Janine Brinkmann-Paulukat, Karin Wisskirchen, Christopher Menne, Elahe Salimi Alizei, Helenie Kefalakes, Martin Theissen, Daniel Hoffmann, Julian Schulze zur Wiesch, Mala K. K. Maini, Markus Cornberg, Anke R. M. Kraft, Verena Keitel, Hans H. H. Bock, Peter A. A. Horn, Robert Thimme, Heiner Wedemeyer, Falko M. M. Heinemann, Tom Luedde, Christoph Neumann-Haefelin, Ulrike Protzer, Joerg Timm
Summary: This study performed a high-resolution analysis of the core(18-27) specific CD8+ T cell and the selected escape pathways in patients with chronic HBV infection. The results demonstrate the promiscuous presentation of the core(18-27) epitope and the selection pressure on the epitope in the context of different HLA class I molecules. Some epitope variants showed evidence for impaired antigen processing and reduced presentation. These findings suggest the importance of considering epitope variants in T cell-based therapy strategies for chronic HBV infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Haruka Miyata, Yoshihiko Hirohashi, Shuhei Yamada, Junko Yanagawa, Aiko Murai, Shinichi Hashimoto, Serina Tokita, Kanta Hori, Takashige Abe, Terufumi Kubo, Tomohide Tsukahara, Takayuki Kanaseki, Nobuo Shinohara, Toshihiko Torigoe
Summary: Recent studies have shown that treatment-resistant cancer stem-like cells can be targeted by cytotoxic T lymphocytes, with a specific antigenic peptide (LMYDAVHVV) derived from GRIK2 being identified as a potential novel target for bladder CSC/CIC immunotherapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Masahiro Matsuki, Yoshihiko Hirohashi, Munehide Nakatsugawa, Aiko Murai, Terufumi Kubo, Shinichi Hashimoto, Serina Tokita, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Sachiyo Nishida, Toshiaki Tanaka, Hiroshi Kitamura, Naoya Masumori, Toshihiko Torigoe
Summary: ICIs are used in cancer immunotherapy to block certain pathways, but low response rates and tumor heterogeneity can lead to resistance. This study found that the specificity of TILs in RCC may be related to gene mutations and reactivity, suggesting heterogenous tumors may have diverse gene mutations and responses to TILs.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Takahito Wakamiya, Yoshihiko Hirohashi, Aiko Murai, Junko Yanagawa, Yuka Mizue, Terufumi Kubo, Shinichi Hashimoto, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Sachiyo Nishida, Yasuo Kohjimoto, Isao Hara, Toshihiko Torigoe
Summary: The ALDH1-high prostate cancer stem-like cells (CSCs) exhibit heterogeneity in tumorigenicity and resistance to radiation and chemotherapy, along with lower levels of phosphorylated AKT. Insulin can activate AKT signaling in these cells, leading to resistance to radiation and chemotherapy. These findings suggest a potential mechanism for treatment resistance in prostate cancer.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Radiology, Nuclear Medicine & Medical Imaging
Masanori Someya, Yuki Fukushima, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Yoh Kozuka, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-Ichi Sakata
Summary: This review discusses the application of radiotherapy for human papillomavirus (HPV)-related cancer and the mechanism of tumor immunity. It also explores how chemoradiotherapy can improve the efficacy of tumor immunity. Additionally, it highlights the usefulness of tumor immunity-related proteins as predictive markers of radiotherapy response, and provides an overview of ongoing clinical trials of combinations of immune checkpoint inhibitors and radiotherapy.
JAPANESE JOURNAL OF RADIOLOGY
(2022)
Article
Oncology
Yuta Nambu, Tasuku Mariya, Shota Shinkai, Mina Umemoto, Hiroko Asanuma, Ikuma Sato, Yoshihiko Hirohashi, Toshihiko Torigoe, Yuichi Fujino, Tsuyoshi Saito
Summary: This study developed a fast and accurate system for detecting and classifying atypical cell clusters using two different deep learning algorithms. The combination of YOLOv4 and ResNeSt algorithms allowed the system to effectively handle overlapping and crowded cell images, achieving high accuracy in cell detection and classification.
Article
Oncology
Koji Nagaoka, Changbo Sun, Yukari Kobayashi, Takayuki Kanaseki, Serina Tokita, Toshihiro Komatsu, Kazuhiro Maejima, Junichiro Futami, Sachiyo Nomura, Keiko Udaka, Hidewaki Nakagawa, Toshihiko Torigoe, Kazuhiro Kakimi
Summary: Despite the success of immune checkpoint inhibitors (ICI) in treating solid cancers, most gastric cancer patients are resistant to ICI monotherapies. This study characterized two murine gastric cancer cell lines, YTN2 and YTN16, and identified new antigens. The findings suggest that combination immunotherapy can effectively inhibit gastric cancer growth, providing a basis for the development of novel combination immunotherapies.
Article
Gastroenterology & Hepatology
Masahito Kawazu, Toshihide Ueno, Koichi Saeki, Nicolas Sax, Yosuke Togashi, Takayuki Kanaseki, Keigo Chida, Fumishi Kishigami, Kazuhito Sato, Shinya Kojima, Masafumi Otsuka, Akihito Kawazoe, Hitomi Nishinakamura, Maeda Yuka, Yoko Yamamoto, Kazuo Yamashita, Satoshi Inoue, Tokiyoshi Tanegashima, Daisuke Matsubara, Kenta Tane, Yosuke Tanaka, Hisae Iinuma, Yojiro Hashiguchi, Shoichi Hazama, Seik-Soon Khor, Katsushi Tokunaga, Masahiro Tsuboi, Toshiro Niki, Masatoshi Eto, Kohei Shitara, Toshihiko Torigoe, Soichiro Ishihara, Hiroyuki Aburatani, Hiroshi Haeno, Hiroyoshi Nishikawa, Hiroyuki Mano
Summary: This study analyzed mutations in HLA-ABC genes in colorectal cancers and found a subtype of tumors with reduced lymphocyte infiltration due to decreased expression of HLA-ABC genes. Patients with these tumors had shorter survival time, despite having a higher tumor mutation burden, suggesting a counterbalance between immunogenic effects and weakened immunoreactivity. Various genetic and epigenetic alterations led to reduced expression of HLA-ABC genes.
Article
Oncology
Takashi Sasaya, Terufumi Kubo, Kenji Murata, Yuka Mizue, Kenta Sasaki, Junko Yanagawa, Makoto Imagawa, Hirotaka Kato, Tomohide Tsukahara, Takayuki Kanaseki, Yasuaki Tamura, Akihiro Miyazaki, Yoshihiko Hirohashi, Toshihiko Torigoe
Summary: This study investigates the effects of cisplatin on the immunotherapy response of oral squamous cell carcinoma (OSCC) and finds that cisplatin increases the surface levels of PD-L1 on OSCC cells but does not alter gene and total protein expression levels. Moreover, cisplatin-induced PD-L1 attenuates the cytotoxic T lymphocyte reaction to OSCC.
Article
Biochemistry & Molecular Biology
Hanae Ichioka, Yoshihiko Hirohashi, Tatsuya Sato, Masato Furuhashi, Megumi Watanabe, Yosuke Ida, Fumihito Hikage, Toshihiko Torigoe, Hiroshi Ohguro
Summary: To investigate the molecular mechanisms responsible for aberrant expression of recoverin (Rec) in cancer cells, Rec-negative lung adenocarcinoma cells (A549) were transfected with a human recoverin cDNA plasmid (A549 Rec) or an empty plasmid (A549 MOCK). The A549 Rec cells showed increased sensitivity to anti-tumor agents, altered cellular metabolism, and formation of larger and stiffer 3D spheroids compared to A549 MOCK. RNA sequencing analysis suggested that aberrantly expressed Rec may be associated with G-protein-coupled receptor (GPCR)-mediated signaling and the cAMP response element binding protein (CREB) signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Bernhard Mlecnik, Alessandro Lugli, Gabriela Bindea, Florence Marliot, Carlo Bifulco, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T. Rau, Martin D. Berger, Iris D. Nagtegaal, Elisa Vink-Borger, Arndt Hartmann, Carol Geppert, Julie Kolwelter, Susanne Merkel, Robert Grutzmann, Marc Van den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Leonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H. A. Roehrl, Pamela S. Ohashi, Linh T. Nguyen, SeongJun Han, Heather L. MacGregor, Sara Hafezi-Bakhtiari, Bradly G. Wouters, Giuseppe Masucci, Emilia K. Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Benedicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn van de Water, Shannon Van Lent-van Vliet, Nikki Knijn, Ana-Maria Musing, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Prabhu Patel, Hemangini H. Vora, Birva Shah, Jayendrakumar B. Patel, Kruti N. Rajvik, Shashank J. Pandya, Shilin N. Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M. Marincola, Paolo A. Ascierto, Bernard A. Fox, Franck Pages, Jerome Galon
Summary: This study found that the immune system status is a better predictor of prognosis in early-stage colon cancer patients than tumor cell-related parameters. The consensus Immunoscore accurately identifies early-stage colon cancer patients with different clinical outcomes, regardless of treatment bias.
Article
Oncology
Sho Miyamoto, Yoshihiko Hirohashi, Rena Morita, Akihiro Miyazaki, Kazuhiro Ogi, Takayuki Kanaseki, Kentaro Ide, Jumpei Shirakawa, Tomohide Tsukahara, Aiko Murai, Takashi Sasaya, Kazushige Koike, Shinichiro Kina, Toshihiro Kawano, Takahiro Goto, Edward Hosea Ntege, Yusuke Shimizu, Toshihiko Torigoe
Summary: Despite advances in cancer therapies, the mortality rate of oral cancer has not improved in the past three decades. Oral cancers contain a subpopulation of cancer stem cells (CSCs) that contribute to cancer infiltration, recurrence, metastasis, and drug resistance. Cytotoxic CD8+ T lymphocytes (CTLs) play a crucial role in targeting CSCs and regulating cancer progression. This study investigates the potential of olfactory receptor family 7 subfamily C member 1 (OR7C1) as a target for CSC-targeted immunotherapy in oral cancer and finds that OR7C1 is expressed only in oral CSCs and is effectively recognized by CTLs.
Article
Oncology
Shohei Sekiguchi, Akira Yorozu, Fumika Okazaki, Takeshi Niinuma, Akira Takasawa, Eiichiro Yamamoto, Hiroshi Kitajima, Toshiyuki Kubo, Yui Hatanaka, Koyo Nishiyama, Kazuhiro Ogi, Hironari Dehari, Atsushi Kondo, Makoto Kurose, Kazufumi Obata, Akito Kakiuchi, Masahiro Kai, Yoshihiko Hirohashi, Toshihiko Torigoe, Takashi Kojima, Makoto Osanai, Kenichi Takano, Akihiro Miyazaki, Hiromu Suzuki
Summary: This study demonstrates that aortic carboxypeptidase-like protein (ACLP) is highly expressed in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC) and is activated by cancer cell-induced TGF-β1 signaling pathway. ACLP derived from CAFs enhances migration and infiltration of cancer cells. Furthermore, ACLP is co-expressed with collagen and negatively correlates with tumor infiltration of CD8+ T lymphocytes, suggesting a potential therapeutic target for stromal-targeted therapy and cancer immunotherapy.
Article
Oncology
Joseph Willis, Robert A. Anders, Toshihiko Torigoe, Yoshihiko Hirohashi, Carlo Bifulco, Inti Zlobec, Bernhard Mlecnik, Sandra Demaria, Won-Tak Choi, Pavel Dundr, Fabiana Tatangelo, Annabella Di Mauro, Pamela Baldin, Gabriela Bindea, Florence Marliot, Nacilla Haicheur, Tessa Fredriksen, Amos Kirilovsky, Benedicte Buttard, Angela Vasaturo, Lucie Lafontaine, Pauline Maby, Carine El Sissy, Assia Hijazi, Amine Majdi, Christine Lagorce, Anne Berger, Marc van den Eynde, Franck Pages, Alessandro Lugli, Jerome Galon
Summary: This study compares the performance of a standardized Immunoscore (IS) digital pathology assay to visual examination by expert pathologists. The results show that the IS assay outperforms the pathologists' evaluation in the clinical setting, demonstrating the potential of IS as an immune pathology tool. These findings can contribute to better diagnosis and prognosis of cancer patients and highlight the importance of digital pathology in cancer management.
Article
Medicine, Research & Experimental
Shin Kobayashi, Serina Tokita, Keigo Moniwa, Katsuyuki Kitahara, Hiromichi Iuchi, Kazuhiko Matsuo, Hidehiro Kakizaki, Takayuki Kanaseki, Toshihiko Torigoe
Summary: CD8+ T cells can recognize and eliminate tumor cells by targeting tumor antigens displayed by HLA class I molecules. In this study, the presence of immunogenic hERV antigens in renal cell carcinoma tissues was identified, and their potential clinical applications in patients with RCC were suggested.
Review
Immunology
Terufumi Kubo, Yoshihiko Hirohashi, Tomohide Tsukahara, Takayuki Kanaseki, Kenji Murata, Rena Morita, Toshihiko Torigoe
Summary: Despite the success of cancer immunotherapy using immune checkpoint inhibitors, the nonspecific release of immunosuppressive mechanisms can lead to immune-related adverse events (irAEs) that significantly impact patients' quality of life. Proper management of irAEs is crucial for the advancement of reliable cancer immunotherapies. IrAEs resemble autoimmune diseases but often have distinct features, and while the detailed pathogenesis remains unclear, numerous studies are providing insights into this phenomenon.
IMMUNOLOGICAL MEDICINE
(2022)