Article
Oncology
Yoshiyasu Umeda, Shusuke Yoshikawa, Yukiko Kiniwa, Takeo Maekawa, Osamu Yamasaki, Taiki Isei, Shigeto Matsushita, Motoo Nomura, Yasuo Nakai, Satoshi Fukushima, Shintaro Saito, Tatsuya Takenouchi, Ryo Tanaka, Hiroshi Kato, Atsushi Otsuka, Taisuke Matsuya, Natsuki Baba, Kotaro Nagase, Takashi Inozume, Takehiro Onuma, Yutaka Kuwatsuka, Noriki Fujimoto, Takahide Kaneko, Masazumi Onishi, Kenjiro Namikawa, Naoya Yamazaki, Yasuhiro Nakamura
Summary: The study found that the combination of radiotherapy (RT) with immune checkpoint inhibitors (ICIs) did not result in a significant survival benefit for patients with mucosal melanoma (MUM), although it may help improve local tumor control and relieve local symptoms.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Multidisciplinary Sciences
Diwakar Davar, Amiran K. Dzutsev, John A. McCulloch, Richard R. Rodrigues, Joe-Marc Chauvin, Robert M. Morrison, Richelle N. Deblasio, Carmine Menna, Quanquan Ding, Ornella Pagliano, Bochra Zidi, Shuowen Zhang, Jonathan H. Badger, Marie Vetizou, Alicia M. Cole, Miriam R. Fernandes, Stephanie Prescott, Raquel G. F. Costa, Ascharya K. Balaji, Andrey Morgun, Ivan Vujkovic-Cvijin, Hong Wang, Amir A. Borhani, Marc B. Schwartz, Howard M. Dubner, Scarlett J. Ernst, Amy Rose, Yana G. Najjar, Yasmine Belkaid, John M. Kirkwood, Giorgio Trinchieri, Hassane M. Zarour
Summary: The study demonstrated that fecal microbiota transplantation combined with anti-PD-1 therapy can overcome resistance to anti-PD-1 in a subset of PD-1 refractory melanoma patients, leading to clinical benefits. This approach induced changes in the gut microbiome and reprogrammed the tumor microenvironment, ultimately enhancing the efficacy of anti-PD-1 treatment.
Article
Oncology
Philippe Saiag, Rafaele Molinier, Anissa Roger, Blandine Boru, Yves Otmezguine, Joelle Otz, Charles-Ambroise Valery, Astrid Blom, Christine Longvert, Alain Beauchet, Elisa Funck-Brentano
Summary: This study demonstrates that the combination of radiotherapy and anti-PD-1 treatment has a high complete response rate in melanoma patients, and radiotherapy can improve progression-free and overall survival in patients who failed anti-PD-1 monotherapy.
Article
Multidisciplinary Sciences
Julien Rossignol, Zakia Belaid, Guillemette Fouquet, Flavia Guillem, Rachel Rignault, Pierre Milpied, Amedee Renand, Tereza Coman, Maud D'Aveni, Michael Dussiot, Elia Colin, Jonathan Levy, Caroline Carvalho, Nicolas Goudin, Nicolas Cagnard, Francine Cote, Joel Babdor, Kanit Bhukhai, Laura Polivka, Amelie E. Bigorgne, Heloise Halse, Aurelien Marabelle, Severine Mouraud, Yves Lepelletier, Thiago T. Maciel, Marie-Therese Rubio, Delphine Heron, Caroline Robert, Isabelle Girault, Doris Lebeherec, Jean-Yves Scoazec, Ivan Moura, Louise Condon, Mirjana Weimershaus, Franck Pages, Jean Davoust, David Gross, Olivier Hermine
Summary: Targeting immune checkpoints, such as PD1, has improved survival in cancer patients. However, most patients still relapse or are refractory to these therapies. This study found that NRP1, a transmembrane glycoprotein, plays a crucial role in modulating the activity of CD8(+) T cells in the antitumor immune response.
Article
Oncology
Cathrine Lund Lorentzen, Julie Westerlin Kjeldsen, Eva Ehrnrooth, Mads Hald Andersen, Inge Marie Svane
Summary: Summary: This study presented the long-term follow-up results of the IDO/PD-L1 vaccine and nivolumab combination therapy in cohort A, showing promising efficacy with high overall response rates and durable responses. However, cohort B did not show significant clinical effects.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Ines Pires da Silva, Tasnia Ahmed, Irene L. M. Reijers, Alison M. Weppler, Allison Betof Warner, James Randall Patrinely, Patricio Serra-Bellver, Clara Allayous, Joanna Mangana, Khang Nguyen, Lisa Zimmer, Claudia Trojaniello, Dan Stout, Megan Lyle, Oliver Klein, Camille L. Gerard, Olivier Michielin, Andrew Haydon, Paolo A. Ascierto, Matteo S. Carlino, Celeste Lebbe, Paul Lorigan, Douglas B. Johnson, Shahneen Sandhu, Serigne N. Lo, Christian U. Blank, Alexander M. Menzies, Georgina V. Long
Summary: The study indicates that for patients resistant to anti-PD-(L)1, ipilimumab plus anti-PD-1 appears to offer higher efficacy compared to ipilimumab monotherapy, with a higher objective response rate, prolonged progression-free survival, longer overall survival, and a similar rate of grade 3-5 toxicity.
Review
Biochemistry & Molecular Biology
Hikaru Nanamori, Yu Sawada
Summary: Malignant melanoma is a skin cancer with unfavorable clinical behavior, and immunotherapy is currently used for treatment. However, not all patients can benefit from this therapy. To overcome this limitation, clinicians have focused on epigenetic modification, which may have additional therapeutic efficacy by regulating gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
John A. McCulloch, Diwakar Davar, Richard R. Rodrigues, Jonathan H. Badger, Jennifer R. Fang, Alicia M. Cole, Ascharya K. Balaji, Marie Vetizou, Stephanie M. Prescott, Miriam R. Fernandes, Raquel G. F. Costa, Wuxing Yuan, Rosalba Salcedo, Erol Bahadiroglu, Soumen Roy, Richelle N. DeBlasio, Robert M. Morrison, Joe-Marc Chauvin, Quanquan Ding, Bochra Zidi, Ava Lowin, Saranya Chakka, Wentao Gao, Ornella Pagliano, Scarlett J. Ernst, Amy Rose, Nolan K. Newman, Andrey Morgun, Hassane M. Zarour, Giorgio Trinchieri, Amiran K. Dzutsev
Summary: An integrated analysis of microbiome and host cell transcriptional data in patients with melanoma treated with anti-PD-1 therapy reveals new associations between streptococcus species and immune-related adverse effects. The study also identifies consistent microbiome associations with clinical outcomes. The results show that baseline microbiota composition is optimally associated with clinical outcome one year after treatment initiation. Meta-analysis and bioinformatic analyses reveal that bacteria associated with favorable response are within the Actinobacteria phylum and Lachnospiraceae/Ruminococcaceae families of Firmicutes. Gram-negative bacteria, on the other hand, are associated with an inflammatory host intestinal gene signature and unfavorable outcome. Two different microbial signatures, enriched for Lachnospiraceae spp. and Streptococcaceae spp., are associated with favorable and unfavorable clinical response, respectively, along with distinct immune-related adverse effects. Supervised learning algorithms consistently predict treatment outcomes in all cohorts, despite heterogeneity between cohorts. The study provides valuable insights into the complex interaction between gut microbiome and response to cancer immunotherapy, paving the way for future research.
Editorial Material
Oncology
Ryan C. Augustin, Jason J. Luke
Summary: This article discusses the 5-year update of the pivotal trial CheckMate-238 and provides context to its results considering limited survival data, neoadjuvant therapy, next-generation biomarkers, and novel immunotherapy combinations.
CLINICAL CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Changsheng Huang, Shengxiang Ren, Yaqi Chen, Anyi Liu, Qi Wu, Tao Jiang, Panjing Lv, Da Song, Fuqing Hu, Jingqing Lan, Li Sun, Xue Zheng, Xuelai Luo, Qian Chu, Keyi Jia, Yan Li, Jun Wang, Caicun Zou, Junbo Hu, Guihua Wang
Summary: This research discovered that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Additionally, PD-L1 K162 methylation controlled the PD1/PD-L1 interaction and significantly enhanced the suppression of T cell activity in controlling cancer immune surveillance. The study demonstrated that PD-L1 hypermethylation was the key mechanism for anti-PD-L1 therapy resistance, identified PD-L1 K162 methylation as a negative predictive marker for anti-PD-1 treatment in patients with non-small cell lung cancer, and showed that the PD-L1 K162 methylation:PD-L1 ratio was a more accurate biomarker for predicting anti-PD-(L)1 therapy sensitivity.
Article
Biochemistry & Molecular Biology
Daniella Kuzmanovszki, Norbert Kiss, Bela Toth, Tunde Kerner, Veronika Toth, Jozsef Szakonyi, Kende Lorincz, Judit Harsing, Eleonora Imredi, Alexa Pfund, Akos Szabo, Valentin Brodszky, Fanni Rencz, Peter Hollo
Summary: Real-world evidence is crucial for assessing the effectiveness and safety of novel therapies. This study analyzed treatment data from patients with advanced melanoma and found that the occurrence of immune-related adverse events (irAEs) was associated with the response to PD-1 ICI therapy, leading to improved overall survival and progression-free survival.
Article
Oncology
Hikmat H. Assi, Chihunt Wong, Kimberly A. Tipton, Li Mei, Ken Wong, Jennifer Razo, Chanty Chan, Bruce Howng, Jason Sagert, Michael Krimm, Linnea Diep, Andrew Jang, Margaret T. Nguyen, Nicole Lapuyade, Victoria Singson, Ruth Villanueva, Madan Paidhungat, Shouchun Liu, Vangipuram Rangan, Olga Vasiljeva, James W. West, Jennifer H. Richardson, Bryan Irving, Dylan Daniel, Marcia Belvin, W. Michael Kavanaugh
Summary: Using protease-activatable antibody prodrugs (Pb-Tx) to locally inhibit PD-1/PD-L1 can reduce systemic immune toxicity while eliciting potent anti-tumor immune responses.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Multidisciplinary Sciences
Irena Wieleba, Kamila Wojas-Krawczyk, Izabela Chmielewska, Magdalena Wojcik-Superczynska, Pawel Krawczyk, Janusz Milanowski
Summary: "Lung adenocarcinoma is the most common subtype of nonsmoker's non-small cell lung cancer. Immune checkpoint inhibitors have been introduced to improve progression-free and overall survival times, but their benefits are not universal. Nivolumab, a monoclonal antibody against the PD-1 protein, is widely used in cancer therapy, but its side effects are a significant concern. Our preliminary study aims to analyze the effect of different concentrations of nivolumab on T lymphocytes to identify an appropriate concentration that achieves clinical activity with minimal side effects."
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Yasuhiro Nakamura, Kenjiro Namikawa, Yukiko Kiniwa, Hiroshi Kato, Osamu Yamasaki, Shusuke Yoshikawa, Takeo Maekawa, Shigeto Matsushita, Tatsuya Takenouchi, Takashi Inozume, Yasuo Nakai, Satoshi Fukushima, Shintaro Saito, Atsushi Otsuka, Noriki Fujimoto, Taiki Isei, Natsuki Baba, Taisuke Matsuya, Ryo Tanaka, Takahide Kaneko, Masazumi Onishi, Yutaka Kuwatsuka, Kotaro Nagase, Takehiro Onuma, Motoo Nomura, Yoshiyasu Umeda, Naoya Yamazaki
Summary: This study compared the efficacy of PD-1 and PD-1+CTLA-4 for the treatment of advanced AM in Japanese patients. The results showed no significant differences in ORR, PFS, and OS between the two groups in PSM patients. In NAM patients, the PD-1+CTLA-4 group had significantly higher ORR and longer PFS, and PD-1+CTLA-4 was identified as an independent predictor of favorable PFS in NAM patients.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Emily R. Webb, Julia Moreno-Vincente, Alistair Easton, Silvia Lanati, Martin Taylor, Sonya James, Emily L. Williams, Vikki English, Chris Penfold, Stephen A. Beers, Juliet C. Gray
Summary: This study investigated the immunomodulatory effects of low-dose cyclophosphamide (CPM) and found that CPM can specifically deplete intratumoral T regulatory cells through apoptosis. When combined with anti-PD-1 antibody therapy, therapeutic efficacy is improved. These findings strongly support clinical evaluation of such combination strategies in neuroblastoma.
Article
Dermatology
Kentaro Ohuchi, Ryo Amagai, Tetsuya Ikawa, Yusuke Muto, Yuna Roh, Junko Endo, Takeo Maekawa, Yumi Kambayashi, Yoshihide Asano, Taku Fujimura
Summary: PAI-1 expression is associated with vascular tumor progression and angiogenesis in Cutaneous Angiosarcoma (CAS), promoting the expression of angiogenic factors and facilitating the formation of tumor-derived tube networks.
EXPERIMENTAL DERMATOLOGY
(2023)
Article
Infectious Diseases
Takamitsu Ohnishi, Shinichi Watanabe, Tetsuya Matsumoto, Hiroshi Yotsuyanagi, Junko Sato, Intestu Kobayashi, Shin Iinuma, Takashi Nagayama, Shuichiro Shibuya, Natsuki Ogawa, Ken Iozumi, Yasuyuki Nakajima, Yukiko Kurikawa, Motoko Kobayashi, Koma Matsuo, Hideyuki Ishikawa, Tadamichi Shimizu, Kiyohiro Tsutsui, Tatsuyoshi Kawamura, Ryuhei Okuyama, Mariko Seishima, Yoichi Akita, Chikatoshi Kasugai, Katsuaki Yano, Yasuhiko Tamada, Kimihiko Mizutani, Kenji Kabashima, Nanako Yamada, Masami Ikeda
Summary: The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) did not differ significantly between the present study and the 2013 survey. However, the prevalence of methicillin-resistant coagulase-negative staphylococci (MRCNS) was higher in the present study compared to the 2013 survey. The susceptibility profiles of MRSA and MRCNS to various antibiotics were not significantly different between the two surveys. Continuous monitoring is important for guiding the appropriate treatment of SSTIs.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2023)
Letter
Dermatology
Takayoshi Komatsu-Fujii, Corrine Sison de Jesus, Takashi Nomura, Kenji Kabashima
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Review
Dermatology
Satoshi Fukushima, Azusa Miyashita, Haruka Kuriyama, Toshihiro Kimura, Satoru Mizuhashi, Yosuke Kubo, Satoshi Nakahara, Hisashi Kanemaru, Nobuhiro Tsuchiya, Hiroaki Mashima, Rong Zhang, Yasushi Uemura
Summary: Cancer immunotherapy is the primary treatment for unresectable cancers, but it is not a complete cure for all patients. Immune cell therapy, specifically using immune cells generated from induced pluripotent stem cells (iPSCs), shows promise for innovative cancer immunotherapy methods. iPSC-derived dendritic cells (iPS-DCs) can activate T cells, while iPSC-derived macrophages (iPS-MPs) attack cancer cells. iPSCs offer a source for genetic modification and addition of immune functions. Additionally, immortalized iPS-DCs and iPS-MPs could potentially reduce costs through mass production. This review summarizes the achievements and future prospects of cancer research using iPS-DCs and iPS-MPs.
EXPERIMENTAL DERMATOLOGY
(2023)
Letter
Dermatology
Tomohiro Ishino, Tselmeg Mijiddorj Myangat, Soichiro Sawamura, Ikko Kajihara, Shuichi Shimada, Hisashi Kanemaru, Kayo Kashiwada-Nakamura, Katsunari Makino, Shinichi Masuguchi, Satoshi Fukushima
JOURNAL OF DERMATOLOGY
(2023)
Article
Dermatology
Hidehisa Saeki, Masashi Akiyama, Masatoshi Abe, Atsuyuki Igarashi, Shinichi Imafuku, Yukihiro Ohya, Norito Katoh, Hideto Kameda, Kenji Kabashima, Yuichiro Tsunemi, Michihiro Hide, Mamitaro Ohtsuki
Summary: This guidance provides information on the use of oral JAK inhibitors for the treatment of atopic dermatitis. It explains the role of oral JAK inhibitors in inhibiting the signal transduction of cytokines involved in the pathogenesis of atopic dermatitis. It also highlights the authorized oral JAK inhibitors for atopic dermatitis in Japan and emphasizes the importance of considering disease factors, treatment factors, and patient backgrounds in the selection of treatment options.
JOURNAL OF DERMATOLOGY
(2023)
Review
Dermatology
R. Bissonnette, L. F. Eichenfield, E. Simpson, D. Thaci, K. Kabashima, J. P. Thyssen, E. Guttman-Yassky, F. P. Nunes, M. Gamalo, F. Ahmad, M. Kuligowski, K. Sun, C. Pipper, A. W. Christensen, P. D'Angelo, M. Milutinovic, A. Guettner, J. I. Silverberg
Summary: Despite the lack of guidelines for analyzing clinical trial data in atopic dermatitis (AD), using the estimand framework can help standardize the analysis and incorporate intercurrent events. Intercurrent events, such as rescue therapy and sleep deprivation, frequently occur in AD trials and their inconsistent handling limits result interpretation. Applying the estimand framework, as guided by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), can improve AD trial design and analysis by providing more reflective and informative results for clinicians to make treatment selection.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Medicine, General & Internal
Emma Guttman-Yassky, Eric L. Simpson, Kristian Reich, Kenji Kabashima, Ken Igawa, Tetsuya Suzuki, Hirotaka Mano, Takeshi Matsui, Ehsanollah Esfandiari, Masutaka Furue
Summary: This study evaluated the efficacy and safety of the anti-OX40 antibody rocatinlimab in patients with moderate-to-severe atopic dermatitis. The results showed significant reductions in EASI score at week 16 in patients receiving rocatinlimab compared to placebo. The treatment led to progressive improvements in atopic dermatitis, which were maintained in most patients after treatment discontinuation, and it was well tolerated.
Article
Dermatology
Amy S. Paller, Jonathan I. Silverberg, Michael J. Cork, Emma Guttman-Yassky, Benjamin Lockshin, Alan D. Irvine, Moon Bum Kim, Kenji Kabashima, Zhen Chen, Yufang Lu, Ashish Bansal, Ana B. Rossi, Arsalan Shabbir
Summary: This study assessed the efficacy and safety of dupilumab in patients with severe erythrodermic atopic dermatitis (AD). The results showed that dupilumab significantly improved AD signs and symptoms, including affected body surface area, Eczema Area and Severity Index (EASI) score, and Pruritus Numerical Rating Scale (PP-NRS) score. The treatment also led to reductions in serum biomarker levels.
Article
Dermatology
Taku Fujimura, Takeo Maekawa, Hiroshi Kato, Takamichi Ito, Shigeto Matsushita, Koji Yoshino, Yasuhiro Fujisawa, Shoichiro Ishizuki, Kojiro Segawa, Jun Yamamoto, Akira Hashimoto, Yumi Kambayashi, Yoshihide Asano
Summary: This study retrospectively evaluated the efficacy and safety profiles of taxane-switch, eribulin methylate, and pazopanib regimens in second-line chemotherapy for taxane-resistant cutaneous angiosarcoma (CAS) patients. Although there was no significant difference in progression-free survival among the regimens, the incidence of all adverse events, as well as severe G3 or more adverse events, was significantly higher in the eribulin methylate group and pazopanib group compared to the taxane-switch group. Therefore, switching to another taxane should be considered for the treatment of taxane-resistant CAS in second-line therapy based on the safety profiles.
JOURNAL OF DERMATOLOGY
(2023)
Article
Dermatology
Kenji Kabashima, Takayo Matsumura, Hiroshi Komazaki, Makoto Kawashima
Summary: This study investigated the impact of nemolizumab on the quality of life in patients with atopic dermatitis. The results showed that nemolizumab treatment improved sleep quality, interpersonal relationships, and work activities.
DERMATOLOGY AND THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Azusa Saika, Prabha Tiwari, Takahiro Nagatake, Eri Node, Koji Hosomi, Tetsuya Honda, Kenji Kabashima, Jun Kunisawa
Summary: Mead acid can suppress retinol-induced irritant contact dermatitis and prevent keratinocyte hyperproliferation and the expression of neutrophil chemoattractants through the PPAR-alpha pathway.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Immunology
Toshiaki Kogame, Gyohei Egawa, Kenji Kabashima
Summary: Recent studies have shown that Janus kinase (JAK) plays a crucial role in signal transduction for inflammatory diseases like atopic dermatitis (AD). Clinical trials using JAK inhibitors and biologic reagents have been successful in treating AD, indicating the efficacy of molecular-based therapies. However, there are concerns about the safety of JAK inhibitors, including severe heart disease. This article provides an overview of the molecular mechanisms of AD and discusses JAK-related biology as a target for AD treatment.
IMMUNOLOGICAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Chikako Senju, Yuka Nakazawa, Taichi Oso, Mayuko Shimada, Kana Kato, Michiko Matsuse, Mariko Tsujimoto, Taro Masaki, Yasushi Miyazaki, Satoshi Fukushima, Satoshi Tateishi, Atsushi Utani, Hiroyuki Murota, Katsumi Tanaka, Norisato Mitsutake, Shinichi Moriwaki, Chikako Nishigori, Tomoo Ogi
Summary: Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by photosensitivity and a high risk of skin tumors due to DNA repair deficiency. This study identified two deep intronic mutations in the ERCC4/XPF gene in 17 cases of XP-F, a rare subtype of XP. These mutations result in reduced gene expression and early-onset skin cancers, highlighting the need for attention to these variants. Additionally, antisense oligonucleotides designed for these mutations can restore DNA repair capacity, suggesting potential therapeutic targets for XP-F.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Dermatology
Hitomi Nakaizumi, Naotomo Kambe, Hiroyuki Irie, Yo Kaku, Masakazu Fujimoto, Hajime Yoshifuji, Yasuhiro Kazuma, Kazumoto Katagiri, Takuro Kanekura, Kenji Kabashima
Summary: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by bone pain, recurrent fever, and other symptoms. A key feature of the syndrome is the presence of a persistent urticarial-like rash. Histopathological data suggests that neutrophilic epitheliotropism, or the tendency of neutrophils to infiltrate and affect epithelial tissue, can be a useful marker for diagnosing SchS and differentiating it from conventional urticaria. Understanding this characteristic is crucial for early diagnosis and appropriate treatment.
JOURNAL OF DERMATOLOGY
(2023)