Article
Immunology
Ryan Zander, Moujtaba Y. Kasmani, Yao Chen, Paytsar Topchyan, Jian Shen, Shikan Zheng, Robert Burns, Jennifer Ingram, Can Cui, Nikhil Joshi, Joseph Craft, Allan Zajac, Weiguo Cui
Summary: This study found that CD4(+) T cells consist of three distinct subsets during chronic viral infection, and IL-21 derived from Tfh cells is critical for sustaining CD8(+) T cell responses and viral control.
Article
Oncology
J. R. Rivas, Y. Liu, S. S. Alhakeem, J. M. Eckenrode, F. Marti, J. P. Collard, Y. Zhang, K. A. Shaaban, N. Muthusamy, G. C. Hildebrandt, R. A. Fleischman, L. Chen, J. S. Thorson, M. Leggas, S. Bondada
Summary: In CLL, T-cell dysfunction is driven by molecules like PD-L1 and IL-10. Suppressing IL-10 using a novel inhibitor enhances antitumor T-cell activity and responses to ICB. Targeting IL-10 provides a novel strategy to improve immunotherapies in CLL patients who do not respond well to current therapies.
Article
Immunology
Arshi Khanam, Natarajan Ayithan, Lydia Tang, Bhawna Poonia, Shyam Kottilil
Summary: Chronic Hepatitis B affects over 350 million people worldwide, and current treatments do reduce complications but do not provide a cure. Humoral responses in CHB rely on T-FH cells to support B cell response, with IL-21 playing a key role. However, defective T-FH cells in CHB can efficiently support B cell responses by producing IL-27, which aids in viral clearance and improving antibody production.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Hironobu Asao
Summary: IL-21 is a cytokine that plays a crucial role in regulating immune responses, autoimmune and inflammatory diseases, and is mainly produced by CD4(+) T cells. It is important for the activation of CD8(+) T cells and has been shown to help recover the function of exhausted CD8(+) T cells caused by chronic microbial infections and cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Arianne C. Richard
Summary: The advent of technologies that can characterize individual cells has revealed extensive diversity between cells of the same subset, including CD8(+) T cells. This review focuses on heterogeneity in CD8(+) T cell responses, particularly the impact of TCR stimulation strength and the mechanisms underlying variation between cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
David O. 'Sullivan, Michal A. Stanczak, Matteo Villa, Franziska M. Uhl, Mauro Corrado, Ramon I. Klein Geltink, David E. Sanin, Petya Apostolova, Nisha Rana, Joy Edwards-Hicks, Katarzyna M. Grzes, Agnieszka M. Kabat, Ryan L. Kyle, Mario Fabri, Jonathan D. Curtis, Michael D. Buck, Annette E. Patterson, Annamaria Regina, Cameron S. Field, Francesc Baixauli, Daniel J. Puleston, Edward J. Pearce, Robert Zeiser, Erika L. Pearce
Summary: Fever can enhance metabolic activity and effector functions of activated CD8* T cells, with limited effects on proliferation or activation marker expression. Exposure to 39 degrees Celsius increases mass and metabolism in T cells, with mitochondrial translation playing a crucial role in the enhanced metabolic activity and function observed.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Medicine, General & Internal
Maike Hofmann, Catrin Tauber, Nina Hensel, Robert Thimme
Summary: CD8(+) T cell responses play a crucial role in chronic HCV infection and HCC, strong virus-specific CD8(+) T cell responses contribute to virus clearance while failure leads to chronic infection development. Tumor-associated and tumor-specific CD8(+) T cells are considered potential targets for immunotherapeutic strategies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cell Biology
Melissa G. Lechner, Zikang Zhou, Aline T. Hoang, Nicole Huang, Jessica Ortega, Lauren N. Scott, Ho -Chung Chen, Anushi Y. Patel, Rana Yakhshi-Tafti, Kristy Kim, Willy Hugo, Pouyan Famini, Alexandra Drakaki, Antoni Ribas, Trevor E. Angell, Maureen A. Su
Summary: Autoimmune toxicity is an increasing challenge in using immune checkpoint inhibitors for cancer treatment. This study investigated the immune infiltrates in ICI-thyroiditis patients and identified a dominant population of cytotoxic CD8+ T cells. The researchers also found that interleukin-21 played a crucial role in the formation of these thyrotoxic CD8+ T cells and validated the findings in a mouse model. These findings provide insights into the mechanisms and potential therapeutic targets for individuals with IRAEs.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Ryo Koyama-Nasu, Motoko Y. Kimura, Masahiro Kiuchi, Ami Aoki, Yangsong Wang, Yukiyoshi Mita, Ichita Hasegawa, Yukihiro Endo, Atsushi Onodera, Kiyoshi Hirahara, Shinichiro Motohashi, Toshinori Nakayama
Summary: This study reveals that CD69 regulates the differentiation process of tumor-specific CD8+ T cells through controlling the expression of transcription factor TOX. Lack of CD69 promotes the generation of functional terminally differentiated CD8+ T cells. Combined use of anti-CD69 and anti-PD-1 shows efficient antitumor effect.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Cell Biology
Pedro Briceno, Elizabeth Rivas-Yanez, Mariana V. Rosemblatt, Brian Parra-Tello, Paula Farias, Leonardo Vargas, Valeska Simon, Cesar Cardenas, Alvaro Lladser, Flavio Salazar-Onfray, Alvaro A. Elorza, Mario Rosemblatt, Maria Rosa Bono, Daniela Sauma
Summary: During CD8+ T cell differentiation, CD73 and adenosine may have an autocrine effect on cytotoxic T cells' metabolic fitness, influencing their functional properties.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Laura Llao-Cid, Philipp M. Roessner, Vicente Chapaprieta, Selcen Oeztuerk, Tobias Roider, Marie Bordas, Ana Izcue, Dolors Colomer, Sascha Dietrich, Stephan Stilgenbauer, Bola Hanna, Jose Ignacio Martin-Subero, Martina Seiffert
Summary: The EOMES SNP is associated with increased risk for CLL due to its negative impact on CD8(+) T-cell-mediated immune control of the disease. EOMES is essential for the expansion and maintenance of CD8(+) T cells, and thus involved in adaptive immune control of CLL.
Article
Gastroenterology & Hepatology
Ajinkya Pattekar, Lena S. Mayer, Chi Wai Lau, Chengyang Liu, Olesya Palko, Meenakshi Bewtra, Hpap Consortium, Lisa C. Lindesmith, Paul D. Brewer-Jensen, Ralph S. Baric, Michael R. Betts, Ali Naji, E. John Wherry, Vesselin T. Tomov
Summary: The study identified immune correlates of NoV protection and persistence and defined the breadth, distribution, and properties of human NoV-specific T-cell immunity, especially in the intestinal mucosa. These findings can guide the development of future vaccines and novel cellular therapeutics.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Oncology
Pedro Velica, Pedro P. Cunha, Nikola Vojnovic, Iosifina Petrina Foskolou, David Bargiela, Milos Gojkovic, Helene Rundqvist, Randall S. Johnson
Summary: By ectopically expressing the HIF transcription factor in CD8(+) T cells, this study demonstrated an enhanced antitumor efficacy against tumor targets. A specific mutation in HIF2 alpha showed the most effective antitumor T cell response, suggesting a potential strategy to increase therapeutic efficacy of CD8(+) T cells.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Immunology
Heather M. Ren, Aron E. Lukacher, Ziaur S. M. Rahman, Nancy J. Olsen
Summary: Elevated interleukin (IL)-21, primarily produced by CD4 T cells, plays a role in promoting effector functions and memory differentiation of CD8 T cells in chronic infections and cancer. Its significance in autoimmune diseases, where the CD4 T cell-derived IL-21:IL21R signaling in CD8 T cells is not fully understood, is still being evaluated.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Gastroenterology & Hepatology
Yan Yan, Wei Zhao, Wei Liu, Yan Li, Xu Wang, Jingna Xun, Chantsalmaa Davgadorj
Summary: CCL19 enhances Ag-responsive IFN-γ(+) CD8(+) T cells in patients with HBV infection and promotes rapid clearance of intrahepatic HBV in mice.
JOURNAL OF GASTROENTEROLOGY
(2021)
Letter
Dermatology
Maxwell Sauder, Marcus Butler
JOURNAL OF CUTANEOUS MEDICINE AND SURGERY
(2022)
Article
Oncology
Michele Maio, Matteo S. Carlino, Anthony M. Joshua, Elaine McWhirter, Antoni Ribas, Paolo A. Ascierto, Wilson H. Miller, Marcus O. Butler, Pier Francesco Ferrucci, Robert R. Zielinski, Michele Del Vecchio, Eduard Gasal, Razi Ghori, Scott J. Diede, Elizabeth Croydon, Omid Hamid
Summary: This study investigated the safety and efficacy of pembrolizumab plus trametinib in solid tumors and BRAF wild-type melanoma. The combination showed limited antitumor activity, with slightly higher efficacy observed in intermittent dosing compared to concurrent dosing.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Jedd D. Wolchok, Vanna Chiarion-Sileni, Rene Gonzalez, Jean-Jacques Grob, Piotr Rutkowski, Christopher D. Lao, C. Lance Cowey, Dirk Schadendorf, John Wagstaff, Reinhard Dummer, Pier Francesco Ferrucci, Michael Smylie, Marcus O. Butler, Andrew Hill, Ivan Marquez-Rodas, John B. A. G. Haanen, Massimo Guidoboni, Michele Maio, Patrick Schoffski, Matteo S. Carlino, Celeste Lebbe, Grant McArthur, Paolo A. Ascierto, Gregory A. Daniels, Georgina Long, Tuba Bas, Corey Ritchings, James Larkin, F. Stephen Hodi
Summary: The 6.5-year results of the CheckMate 067 trial demonstrate durable clinical benefits with nivolumab plus ipilimumab or nivolumab monotherapy compared to ipilimumab alone in patients with advanced melanoma.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Thiago P. Muniz, Daniel V. Araujo, Kerry J. Savage, Tina Cheng, Moumita Saha, Xinni Song, Sabrina Gill, Jose G. Monzon, Debjani Grenier, Sofia Genta, Michael J. Allen, Diana P. Arteaga, Samuel D. Saibil, Marcus O. Butler, Anna Spreafico, David Hogg
Summary: This study describes the characteristics of ICI-induced IDDM in patients treated at five Canadian cancer centers, and observes that presentation with hyperglycemic crisis is common and that patients treated with combination immunotherapy regimens develop ICI-induced IDDM earlier than those treated with monotherapy. ICI-induced IDDM is irreversible but is associated with high tumor response rates and prolonged survival.
Article
Oncology
Richard D. Carvajal, Paul Nathan, Joseph J. Sacco, Marlana Orloff, Leonel F. Hernandez-Aya, Jessica Yang, Jason J. Luke, Marcus O. Butler, Sarah Stanhope, Laura Collins, Cheryl McAlpine, Chris Holland, Shaad E. Abdullah, Takami Sato
Summary: This phase I study successfully defined the recommended phase II dose of tebentafusp for patients with metastatic uveal melanoma, showing manageable side effects and a potential efficacy signal.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
David S. Hong, Marcus O. Butler, Russell K. Pachynski, Ryan Sullivan, Partow Kebriaei, Sarah Boross-Harmer, Armin Ghobadi, Matthew J. Frigault, Ecaterina E. Dumbrava, Amy Sauer, Francine Brophy, Jean-Marc Navenot, Svetlana Fayngerts, Zohar Wolchinsky, Robyn Broad, Dzmitry G. Batrakou, Ruoxi Wang, Luisa M. Solis, Dzifa Yawa Duose, Joseph P. Sanderson, Andrew B. Gerry, Diane Marks, Jane Bai, Elliot Norry, Paula M. Fracasso
Summary: ADP-A2M10 is a safe and effective treatment for malignancies, with detectable presence in peripheral blood and tumor tissues, showing potential therapeutic effects for MAGE-A10 positive tumors.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Diana Paola Arteaga Ceballos, Zaid Saeed-Kamil, Ian King, Tracy Stockley, Diane Liu, Thiago P. Muniz, Samuel D. Saibil, David Hogg, Anna Spreafico, Marcus O. Butler
Summary: This study identified variations in BRAF test results in turnaround time (TAT). One factor affecting this timeline is transfer time, which can be streamlined by pathology reflex testing. Delays in TAT affect the timing and type of therapeutic intervention, especially in patients with stage IV disease.
JCO ONCOLOGY PRACTICE
(2022)
Article
Immunology
Giselle M. Boukhaled, Ramy Gadalla, Heidi J. Elsaesser, Diala Abd-Rabbo, Rene Quevedo, S. Y. Cindy Yang, Mengdi Guo, Ben X. Wang, Babak Noamani, Diana Gray, Sally C. M. Lau, Kirsty Taylor, Kyaw Aung, Anna Spreafico, Aaron R. Hansen, Samuel D. Saibil, Naoto Hirano, Cynthia Guidos, Trevor J. Pugh, Tracy L. McGaha, Pamela S. Ohashi, Adrian G. Sacher, Marcus O. Butler, David G. Brooks
Summary: The authors have developed a method to predict the response to anti-PD1 therapy and long-term survival of cancer patients by scoring the epigenetic imprinting of T cell responsiveness to type 1 interferons. They found that the responsiveness to IFN-Is before treatment was highly predictive of long-term survival, with hyporesponsiveness being associated with better survival and high responsiveness being associated with treatment failure. The study highlights the importance of pre-therapy cellular states in predicting the success of PD1-blocking immunotherapy.
Article
Oncology
Jeffrey S. Weber, Dirk Schadendorf, Michele Del Vecchio, James Larkin, Victoria Atkinson, Michael Schenker, Jacopo Pigozzo, Helen Gogas, Stephane Dalle, Nicolas Meyer, Paolo A. Ascierto, Shahneen Sandhu, Thomas Eigentler, Ralf Gutzmer, Jessica C. Hassel, Caroline Robert, Matteo S. Carlino, Anna Maria Di Giacomo, Marcus O. Butler, Eva Munoz-Couselo, Michael P. Brown, Piotr Rutkowski, Andrew Haydon, Jean-Jacques Grob, Jacob Schachter, Paola Queirolo, Luis de la Cruz-Merino, Andrew Haydon, Jean-Jacques Grob, Jacob Schachter, Paola Queirolo, Luis De La Cruz-Merino, Andre van der Westhuizen, Alexander M. Menzies, Sandra Re, Tuba Bas, Veerle de Pril, Julia Braverman, Daniel J. Tenney, Hao Tang, Georgina Long
Summary: The CheckMate 915 trial compared adjuvant nivolumab plus ipilimumab with nivolumab alone in patients with resected melanoma. The study found that there was no significant difference in recurrence-free survival between the two treatment groups.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Richard D. Carvajal, Marcus O. Butler, Alexander N. Shoushtari, Jessica C. Hassel, Alexandra Ikeguchi, Leonel Hernandez-Aya, Paul Nathan, Omid Hamid, Josep M. Piulats, Matthew Rioth, Douglas B. Johnson, Jason J. Luke, Enrique Espinosa, Serge Leyvraz, Laura Collins, Howard M. Goodall, Koustubh Ranade, Chris Holland, Shaad E. Abdullah, Joseph J. Sacco, Takami Sato
Summary: In a study of previously treated metastatic uveal melanoma patients, treatment with Tebentafusp showed promising clinical activity and acceptable safety profile. Early reduction in circulating tumor DNA was strongly associated with overall survival.
Review
Health Care Sciences & Services
Saeed Moradian, Roma Maguire, Geoffrey Liu, Monika K. Krzyzanowska, Marcus Butler, Chantal Cheung, Marisa Signorile, Nancy Gregorio, Shiva Ghasemi, Doris Howell
Summary: Advances in cancer treatment have led to longer survival for patients, but they still face physical and psychological symptoms. This systematic review aims to assess the effectiveness of eHealth interventions in supporting cancer patients in managing symptoms and improving their quality of life.
JMIR RESEARCH PROTOCOLS
(2023)
Article
Biochemistry & Molecular Biology
Raffit Hassan, Marcus Butler, Roisin E. E. O'Cearbhaill, David Y. Y. Oh, Melissa Johnson, Kevin Zikaras, Munisha Smalley, Michael Ross, Janos L. L. Tanyi, Azam Ghafoor, Nirali N. N. Shah, Babak Saboury, Liang Cao, Alfonso Quintas-Cardama, David Hong
Summary: The T cell receptor fusion construct gavocabtagene autoleucel shows significant anti-tumor activity in patients with treatment-refractory mesothelin-expressing solid tumors. However, it may have a narrow therapeutic window.
Article
Oncology
Maysa Vilbert, Erica C. Koch, April A. N. Rose, Rob C. Laister, Diana Gray, Valentin Sotov, Susanne Penny, Anna Spreafico, Devanand M. Pinto, Marcus O. Butler, Samuel D. Saibil
Summary: Cutaneous melanoma (CM) patients respond better to immune checkpoint inhibitors (ICI) than mucosal and uveal melanoma patients (MM/UM). Aiming to explore these differences and understand the distinct response to ICI, we evaluated the serum metabolome of advanced CM, MM, and UM patients. Our study revealed a distinct metabolomic profile between the most resistant melanoma subtypes, UM and MM, compared to CM. Alterations within the kynurenine pathway, polyamine metabolism, and sphingolipid metabolic pathway may contribute to the poor response to ICI.
Article
Oncology
Erica C. Koch Hein, Maysa Vilbert, Ian Hirsch, Mauricio Fernando Ribeiro, Thiago P. Muniz, Cynthia Fournier, Khaled Abdulalem, Erick F. Saldanha, Erika Martinez, Anna Spreafico, David H. Hogg, Marcus O. Butler, Samuel D. Saibil
Summary: This study evaluated the effectiveness and safety of immune checkpoint inhibitors in treating advanced cutaneous squamous cell carcinoma. The results showed that immune checkpoint inhibitors were effective and safe for patients with this condition, regardless of age, immune status, or performance status. Immune checkpoint inhibitors offer a preferred therapeutic option for patients with comorbidities.
Article
Health Care Sciences & Services
Victoria Federico Paly, Murat Kurt, Lirong Zhang, Marcus O. Butler, Olivier Michielin, Adenike Amadi, Emma Hernlund, Helen M. Johnson, Srividya Kotapati, Andriy Moshyk, John Borrill
Summary: This study evaluated the predictive accuracy of different models in estimating the long-term overall survival benefit of immune checkpoint inhibitor combination therapy in advanced melanoma. The results showed that models explicitly incorporating survival heterogeneity provided more accurate and consistent long-term overall survival estimates.
MDM POLICY & PRACTICE
(2022)