Editorial Material
Immunology
David G. Brooks, Pamela S. Ohashi
Summary: This article reveals how dendritic cells create a niche for the preservation of Tpex cells.
Article
Medicine, Research & Experimental
Camille-Charlotte Balanca, Anna Salvioni, Clara-Maria Scarlata, Marie Michelas, Carlos Martinez-Gomez, Carlos Gomez-Roca, Victor Sarradin, Marie Tosolini, Carine Valle, Frederic Pont, Gwenael Ferron, Laurence Gladieff, Sebastien Vergez, Agnes Dupret-Bories, Eliane Mery, Philippe Rochaix, Jean-Jacques Fournie, Jean-Pierre Delord, Christel Devaud, Alejandra Martinez, Maha Ayyoub
Summary: Tumor antigen-specific CD4 T cells exhibit exhaustion in patients with head and neck, cervical, and ovarian cancer, characterized by high PD-1 and CD39 expression and low cytokine secretion despite functional presence. Terminal exhaustion of CD4 T cells is observed regardless of TIM-3 expression, suggesting divergence from CD8 T cell exhaustion. PD-1 blockade enhances CD4 T cell activation and promotes dendritic cell maturation, leading to improved tumor-specific CD8 T cell proliferation.
Article
Medicine, Research & Experimental
Renpeng Ding, Shang Liu, Shanshan Wang, Huanyi Chen, Fei Wang, Qumiao Xu, Linnan Zhu, Xuan Dong, Ying Gu, Xiuqing Zhang, Cheng-Chi Chao, Qianqian Gao
Summary: The study revealed that differential expressions of tumor PD-L1 can affect the functionality of T cells, leading to increased exhaustion and secretion of both pro-inflammatory and anti-inflammatory cytokines. Increased expression of tumor PD-L1 also modified the gene profiles of chemokines and had distinct effects on inhibitory checkpoint molecules. This suggests that the outcome of PD-L1 intervention may depend on the balance among immune regulatory circuits.
Article
Immunology
Aditya Arra, Holger Lingel, Mandy Pierau, Monika C. C. Brunner-Weinzierl
Summary: PD-1 plays a crucial role in suppressing the differentiation and function of Tc17 cells, and blockade of PD-1 can effectively enhance tumor immune response. PD-1 signaling inhibits the expression of IL-17 and related transcription factors in Tc17 cells, and also suppresses the expression of IL-21 and IL-23 receptors specific to Tc17 cells. Inhibition of PD-1 leads to the conversion of Tc17 cells into Tc1 cells, which possess tumor control characteristics.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Mahdi Abdoli Shadbad, Nima Hemmat, Vahid Khaze Shahgoli, Afshin Derakhshani, Farzad Baradaran, Oronzo Brunetti, Rossella Fasano, Renato Bernardini, Nicola Silvestris, Behzad Baradaran
Summary: By co-administering anti-PD-1 with CAR-T cells and editing the PD-1 gene in CAR-T cells, the survival of animal models can be significantly improved. PD-1 gene-edited CAR-T cells can enhance the survival of animal-bearing gliomas compared to conventional CAR-T cells, regardless of the CAR-T generation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anne-Kathrin Knuth, Arnaud Huard, Zumer Naeem, Peter Rappl, Rebekka Bauer, Ana Carolina Mota, Tobias Schmid, Ingrid Fleming, Bernhard Bruene, Simone Fulda, Andreas Weigert
Summary: The interaction between apoptotic cells and macrophages can significantly affect macrophage proliferation, which may play a critical role in the efficient clearance and resolution of inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Hematology
Margarita Sanchez-Beato
Summary: This study expands the list of potential driver genes in CTCL and demonstrates that PDCD1 deletion can reverse T-cell exhaustion signatures, leading to a worse prognosis.
Article
Multidisciplinary Sciences
Kristiyan Kanev, Patrick Roelli, Ming Wu, Christine Wurmser, Mauro Delorenzi, Michael W. Pfaffl, Dietmar Zehn
Summary: Single-cell RNA-seq offers the opportunity to improve the efficacy of T-cell based immunotherapy. The plate-based method developed by the authors for cytotoxic T cell profiling captures a higher number of transcripts and detects genes with increased dynamic range compared to droplet-based methods.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Yujia Zheng, Hao Zhang, Chu Xiao, Ziqin Deng, Tao Fan, Bo Zheng, Chunxiang Li, Jie He
Summary: The expression of KLF12 in tumors is correlated with resistance to immunotherapy. KLF12 suppresses the infiltration and function of CD8(+) T cells by inhibiting the expression of Gal-1. Targeting the KLF12/Gal-1 pathway may provide a new therapeutic target for patients with immunotherapy resistance.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Mehdi Barati, Farshad Mirzavi, Mahdi Atabaki, Bahram Bibak, Mojgan Mohammadi, Mahmoud Reza Jaafari
Summary: This study examines the use of siRNA delivery systems to target PD-1 and PD-L1, and investigates the anti-cancer mechanisms and challenges associated with siRNA molecules. The findings suggest that suppressing PD-1 in T cells increases T lymphocyte activity, while suppressing PD-L1 in DCs improves antigen presentation and co-stimulatory signals, resulting in T cell activation. Suppression of PD-L1/2 in cancer cells reduces chemotherapy resistance and cancer cell suppression of T cells.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Oncology
Jiang Liu, Degan Liu, Guangyin Hu, Jingjing Wang, Dadong Chen, Chuanjun Song, Yin Cai, Chentong Zhai, Wenjing Xu
Summary: This study investigated the predictive values of circulating CD8(+) T cells and CD8(+)T/CD4(+)T cell ratio in advanced gastric cancer patients receiving immunotherapy. The results showed that patients with higher percentages of CD8(+) T and CD8(+) Tm expressing PD-1, as well as a higher PD-1(+)CD8(+)T/PD-1(+)CD4(+)T cell ratio, had better survival outcomes. These findings provide preliminary evidence for screening the population that would benefit from immunotherapy.
CANCER CELL INTERNATIONAL
(2023)
Review
Allergy
Duncan M. Morgan, Wayne G. Shreffler, J. Christopher Love
Summary: Single-cell RNA sequencing is a powerful tool for studying gene expression and has been widely applied to profile the phenotypes and clonotypes of CD4+ T cells. It allows for the investigation of cellular heterogeneity and interactions between CD4+ T cells and other cells. The technology has great potential to advance our understanding of the roles of CD4+ T cells in health and disease.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Valerie Janelle, Mathieu Neault, Marie-Eve Lebel, Dave Maurice De Sousa, Salix Boulet, Ludovic Durrieu, Cedric Carli, Chloe Muzac, Sebastien Lemieux, Nathalie Labrecque, Heather J. J. Melichar, Frederick A. Mallette, Jean-Sebastien Delisle
Summary: The development of T-cell dysfunction upon repeated antigen exposure involves the accumulation of DNA damage and activation of the p38MAPK signaling pathway, leading to cellular senescence features including p16(INK4a) upregulation. However, targeting p16(INK4a) can improve T-cell functionality in exhausted CAR T cells, suggesting T-cell senescence as a potential target in immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Christiane Majer, Holger Lingel, Aditya Arra, Hans-Gert Heuft, Dirk Bretschneider, Silke Balk, Katrin Vogel, Monika C. Brunner-Weinzierl
Summary: Newborn CD4 T-cells show activation-induced events and produce Th1 cytokines in response to Staphylococcus aureus, indicating their ability to mount immediate and controlled antibacterial responses. The proliferation of neonatal T-helper cells is influenced by sex, IL-2 receptor expression, and the PD-1/PD-L1 axis. In addition, the regulation of multifunctional T-helper cells is exclusively mediated by the PD-1/PD-L1 axis in neonatal CD4 T-cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Kenji Shimizu, Daisuke Sugiura, Il-mi Okazaki, Takumi Maruhashi, Tatsuya Takemoto, Taku Okazaki
Summary: PD-1 preferentially inhibits the expression of TCR-inducible genes when TCR:pMHC affinity is low, demonstrating a qualitative control of T cell responses by suppressing low-affinity T cells. Peptide-MHC affinities and MHC expression levels do not affect PD-1 sensitivity, suggesting that the strength of individual TCR signal is the key determinant of PD-1 sensitivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Michael Peled, Anna S. Tocheva, Sabina Sandigursky, Shruti Nayak, Elliot A. Philips, Kim E. Nichols, Marianne Strazza, Inbar Azoulay-Alfaguter, Manor Askenazi, Benjamin G. Neel, Adam J. Pelzek, Beatrix Ueberheide, Adam Mor
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Biochemistry & Molecular Biology
Fatemeh Rahimi Gharemirshamlu, Maliha Afsar, Taseem A. Mokhdomi, Asif Amin, Shoiab Bukhari, Anbarasu Krishnan, Chundi Vinay Kumar, Kourosh Bamdad, Trupti N. Patel, Raies A. Qadri, Naveed Anjum Chikan, Nadeem Shabir
JOURNAL OF CELLULAR BIOCHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Matthew A. Dragovich, Kieran Adam, Marianne Strazza, Anna S. Tocheva, Michael Peled, Adam Mor
Article
Immunology
M. Strazza, K. Adam, A. Smrcka, S. Lerrer, A. Mor
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2020)
Review
Cell Biology
Marianne Strazza, Adam Mor
Article
Biochemistry & Molecular Biology
Anna S. Tocheva, Michael Peled, Marianne Strazza, Kieran R. Adam, Shalom Lerrer, Shruti Nayak, Inbar Azoulay-Alfaguter, Connor J. R. Foster, Elliot A. Philips, Benjamin G. Neel, Beatrix Ueberheide, Adam Mor
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Asif Amin, Taseem A. Mokhdomi, Shoiab Bukhari, Zubair Wani, Naveed A. Chikan, Basit A. Shah, Aabid M. Koul, Umer Majeed, Faizah Farooq, Ayub Qadri, Raies A. Qadri
Summary: Tumor-associated macrophages (TAMs) play a vital role in promoting tumor growth and metastasis by interacting with tumor cells. A prominent immunogenic protein, EDA(FN), secreted by A549 cells, drives the proinflammatory response and metastatic capacity through its cross-talk with monocytes.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Cell Biology
Marianne Strazza, Kieran Adam, Shalom Lerrer, Johanna Straube, Sabina Sandigursky, Beatrix Ueberheide, Adam Mor
Summary: PD-1 is a critical therapeutic target in cancer immunotherapy, with SHP2 playing a key role in its downstream signaling. Research has found that SHP2 specifically dephosphorylates ITK, which is associated with PD-1 inhibitory cellular functions. ITK may be a unique target in this pathway, and combining ITK inhibitors with PD-1 blockade may improve cancer treatment outcomes.
Article
Multidisciplinary Sciences
Shalom Lerrer, Anna S. Tocheva, Shoiab Bukhari, Kieran Adam, Adam Mor
Summary: Although PD-1 signaling has an inhibitory effect, it can also activate additional functions in T cells; T cells that proliferate more following PD-1 ligation are associated with effector and central memory phenotypes; the presence of transcriptionally and functionally distinct T cell populations responsive to PD-1 ligation provides new insights into the biology of PD-1 and suggests improving clinical outcomes of PD-1 blockade with T cell subset-specific approaches.
Article
Biology
Marianne Strazza, Inbar Azoulay-Alfaguter, Michael Peled, Kieran Adam, Adam Mor
Summary: Strazza et al. demonstrate that PAG is phosphorylated following PD-1 ligation, and its deletion sensitizes tumors to PD-1 blockade. This study suggests that PAG is a critical mediator of PD-1 signaling and a promising target to enhance T cell activation in tumors.
COMMUNICATIONS BIOLOGY
(2021)
Review
Cell Biology
Adam Mor, Marianne Strazza
Summary: The emergence of immune checkpoint inhibitors has transformed the treatment of tumors, but challenges still remain such as non-responsive patients and immune-related adverse events. This review aims to bridge the gap between our understanding of PD-1 signaling, ICI-induced adverse events, and autoimmune diseases, and propose new therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Yevgeniya Gartshteyn, Anca. D. Askanase, Ruijiang Song, Shoiab Bukhari, Matthew Dragovich, Kieran Adam, Adam Mor
Summary: SLAMF6 clustering with the CD3 complex enhances T cell activity and shares downstream signaling pathways. Bispecific antibodies can modulate T cell responses.
LIFE SCIENCE ALLIANCE
(2022)
Review
Immunology
Shoiab Bukhari, Aaron F. Mertz, Shruti Naik
INTERNATIONAL IMMUNOLOGY
(2019)