Editorial Material
Cell Biology
Gregory M. Chen, Jan Joseph Melenhorst, Kai Tan
Summary: CAR T cell therapies targeting CD19 and CD22 have shown success in treating B cell cancers, but not in non-B cell cancers. The interaction between CAR T cells and normal B cells may play a crucial role in determining clinical CAR T cell responses.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Tobias Schatton, Yuta Itoh, Christina Martins, Erik Rasbach, Praveen Singh, Mariana Silva, Kyla Mucciarone, Markus V. Heppt, Jenna Geddes-Sweeney, Kate Stewart, Anne Brandenburg, Jennifer Liang, Charles J. Dimitroff, Martin C. Mihm, Jennifer Landsberg, Christoph Schlapbach, Christine G. Lian, George F. Murphy, Thomas S. Kupper, Matthew R. Ramsey, Steven R. Barthel
Summary: Tim-3 is an intrinsic growth-suppressive receptor in melanoma cells, and blocking it may promote MAPK-dependent tumorigenesis, counteracting the antitumor activity of T-cell-directed Tim-3 inhibition.
Review
Biochemistry & Molecular Biology
Ivan Y. Y. Filin, Yuri P. P. Mayasin, Chulpan B. B. Kharisova, Anna V. Gorodilova, Kristina V. V. Kitaeva, Daria S. S. Chulpanova, Valeriya V. V. Solovyeva, Albert A. A. Rizvanov
Summary: Melanoma is a highly aggressive and therapy-resistant cancer, with increasing incidence rates. Conventional methods of treatment often result in relapse. Adjuvant therapies, such as cell-based immunotherapy, can be used to reduce recurrence risk by mobilizing the immune system to kill cancer cells. This review discusses the advantages, challenges, and ongoing clinical trials of cell-based therapy for adjuvant treatment of melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Y. Erin Chen, Djenet Bousbaine, Alessandra Veinbachs, Katayoon Atabakhsh, Alex Dimas, Victor K. Yu, Aishan Zhao, Nora J. Enright, Kazuki Nagashima, Yasmine Belkaid, Michael A. Fischbach
Summary: Certain bacterial colonists induce a specific T cell response, even in the absence of infection. By engineering a skin bacterium to express tumor antigens, researchers were able to elicit tumor-specific T cells that infiltrate lesions and possess cytotoxic activity. This reveals the potential for commensal bacteria to be harnessed therapeutically for targeted immune responses.
Review
Oncology
Yannick Bulliard, Borje S. Andersson, Mehmet A. Baysal, Jason Damiano, Apostolia M. Tsimberidou
Summary: T cell differentiation and exhaustion play a crucial role in the design and efficacy of CAR-T cell therapy. Understanding the key regulators in T cell biology offers new opportunities for the development of next-generation CAR-T cell therapies.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jihye Hong, Mikyung Kang, Mungyo Jung, Yun Young Lee, Yongbum Cho, Cheesue Kim, Seuk Young Song, Chun Gwon Park, Junsang Doh, Byung-Soo Kim
Summary: While T-cell therapy is a significant breakthrough in cancer immunotherapy, its efficacy against solid tumors is limited due to T-cell exhaustion caused by immunosuppressive mechanisms. T-cell-derived nanovesicles (TCNVs) produced by extrusion through membranes with micro/nanosized pores show promising anti-tumoral activity in the immunosuppressive tumor microenvironment. TCNVs express programmed cell death protein 1 and TGF-beta receptor on their surface, which helps block PD-L1 on cancer cells and scavenge TGF-beta in the TME, preventing T-cell exhaustion and directly killing cancer cells. These findings suggest TCNVs as an effective strategy for cancer immunotherapy to overcome tumor's immunosuppressive mechanisms.
ADVANCED MATERIALS
(2021)
Article
Multidisciplinary Sciences
Hohyun Lee, Yutong Guo, James L. Ross, Scott Schoen, F. Levent Degertekin, Costas Arvanitis
Summary: The study presents a closed-loop controlled, microbubble-enhanced focused ultrasound (MB-FUS) system that enhances the therapeutic impact of immune checkpoint blockade in glioblastomas (GBMs). The system fine-tunes exposure settings to promote the expression of inflammatory markers and delivery of anti-PD1 drugs, resulting in improved survival and the formation of long-lived memory T cells that support tumor rejection.
Article
Multidisciplinary Sciences
Erietta Stelekati, Zhangying Cai, Sasikanth Manne, Zeyu Chen, Jean-Christophe Beltra, Lance Alec Buchness, Xuebing Leng, Svetlana Ristin, Kito Nzingha, Viktoriya Ekshyyan, Christina Niavi, Mohamed S. Abdel-Hakeem, Mohammed-Alkhatim Ali, Sydney Drury, Chi Wai Lau, Zhen Gao, Yuguang Ban, Simon K. Zhou, K. Mark Ansel, Makoto Kurachi, Martha S. Jordan, Alejandro V. Villarino, Shin Foong Ngiow, E. John Wherry
Summary: This study identifies miR-29a as a key regulator of exhausted CD8 T cells (TEX) during chronic viral infection. It shows that miR-29a improves CD8 T cell responses, inhibits exhaustion-driving transcriptional pathways, and regulates ribosomal biogenesis. As a result, miR-29a promotes a memory-like CD8 T cell differentiation state during chronic infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Kevin Roe
Summary: T-cell exhaustion has been extensively studied, while less attention has been given to NK-cell exhaustion and B-cell exhaustion. There are differences and similarities between lymphocyte exhaustion, including NK-cell exhaustion, B-cell exhaustion, and T-cell exhaustion. Lymphocyte exhaustion is often confused with anergy, cellular senescence, and suppression, and it is not a binary state but rather a continuum caused by different levels and duration of continuous antigenic stimulation.
Article
Multidisciplinary Sciences
Kwasi Adu-Berchie, Joshua M. Brockman, Yutong Liu, Tania W. To, David K. Y. Zhang, Alexander J. Najibi, Yoav Binenbaum, Alexander Stafford, Nikolaos Dimitrakakis, Miguel C. Sobral, Maxence O. Dellacherie, David J. Mooney
Summary: In this study, a hydrogel was developed to deliver adoptively transferred T cells to the tumor site and recruit and activate host antigen-presenting cells. The localized cell depots containing T cells showed significantly better control of subcutaneous tumors compared to other delivery methods. The combination of T cell delivery and biomaterial-driven activation of host immune cells prolonged T cell activation and enabled long-term tumor control.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Jonas Leonhard, Matthias Schaier, Florian Kaelble, Martin Zeier, Andrea Steinborn
Summary: Immunosuppressive therapy increases the risk of non-melanoma skin cancer in elderly kidney transplant recipients. The therapy inhibits the differentiation of CD8(+) regulatory T cells more than that of CD8(+) responder T cells, resulting in exhausted Tresp profile and reduced cancer immunity in elderly KTR.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Plant Sciences
Yu Kou, Qidi Sun, Rentao Zhu, Zhijie Lin, Zhuoqun Li, Hairong Xu, Xuan Feng, Yanqing Liu
Summary: The study aimed to find a natural drug monomer that can effectively reverse the polarity of tumor-associated macrophages, inhibit melanoma metastasis, and improve survival time. Dioscin was found to repolarize macrophages from M2 to M1 phenotype and suppress melanoma migration, invasion, and metastasis through activation of Cx43-GJs/IFN-gamma/STAT1 pathway and inhibition of Cx43-GJs/IL-4/JAK2/STAT3 pathway.
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
Biochemistry & Molecular Biology
Thomas Parigger, Franz Josef Gassner, Christian Scherhaeufl, Aryunni Abu Bakar, Jan Philip Hoepner, Alexandra Hoedlmoser, Markus Steiner, Kemal Catakovic, Roland Geisberger, Richard Greil, Nadja Zaborsky
Summary: This study found that a substantial fraction of non-CLL specific T cells in the chronic lymphocytic leukemia mouse model becomes exhausted during disease progression in a bystander effect. These findings have important implications for the general efficacy assessment of immune checkpoint therapies in CLL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Josephine R. Giles, Sasikanth Manne, Elizabeth Freilich, Derek A. Oldridge, Amy E. Baxter, Sangeeth George, Zeyu Chen, Hua Huang, Lakshmi Chilukuri, Mary Carberry, Lydia Giles, Nan-Ping P. Weng, Regina M. Young, Carl H. June, Lynn M. Schuchter, Ravi K. Amaravadi, Xiaowei Xu, Giorgos C. Karakousis, Tara C. Mitchell, Alexander C. Huang, Junwei Shi, E. John Wherry
Summary: This study generated an epigenetic and transcriptional atlas of T cell differentiation from healthy humans and applied it to explore disease-specific biology. The study identified molecular regulations of gene expression and chromatin accessibility during T cell differentiation and provided insights into disease biology through three research settings. The study also successfully predicted genome-wide cis-regulatory elements and validated the approach for functional annotation of key effector genes, demonstrating the potential of identifying targets for non-coding cellular engineering.