Article
Immunology
Jessica M. Sierra, Florencia Secchiari, Sol Y. Nunez, Ximena L. Raffo Iraolagoitia, Andrea Ziblat, Adrian D. Friedrich, Maria V. Regge, M. Cecilia Santilli, Nicolas I. Torres, Mariana Gantov, Aldana Trotta, Carlos Ameri, Gonzalo Vitagliano, Hernando Rios Pita, Luis Rico, Agustin Rovegno, Nicolas Richards, Carolina I. Domaica, Norberto W. Zwirner, Mercedes B. Fuertes
Summary: NK cells in clear cell renal cell carcinoma patients display altered phenotype and impaired effector functions, with a high frequency of tumor-infiltrating PD-L1(+) NK cells suggesting immunoregulatory functions. In vitro studies show that PD-L1(hi) NK cells exhibit an activated phenotype and enhanced effector functions, while also inhibiting CD8(+) T cell proliferation in a PD-L1-dependent manner.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Maria-Luisa Del Rio, Jose-Antonio Perez-Simon, Jose-Ignacio Rodriguez-Barbosa
Summary: The expression of PD-L1 on A20 leukemia tumor cells modulates the interaction between CD8 T cells and tumor-specific antigens, but does not inhibit NK cell-mediated hybrid resistance.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Aixian Zheng, Yanlin Du, Yiru Wang, Youshi Zheng, Zhaoyu Ning, Ming Wu, Cuilin Zhang, Da Zhang, Jingfeng Liu, Xiaolong Liu
Summary: This study introduces a highly stable CD16/PDL1 bi-specific aptamer (CP-bi-apt) that enhances the immune response of NK cells against tumors and reduces the negative impact of PD-L1 over-expression.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Chemistry, Multidisciplinary
Kieu Lam, Ada Leung, Alan Martin, Mark Wood, Petra Schreiner, Lorne Palmer, Owen Daly, Wenchen Zhao, Kevin McClintock, James Heyes
Summary: A new ionizable lipid (Lipid 10) has been discovered to improve the efficacy and tolerability of lipid nanoparticles, making them highly effective in delivering nucleic acid therapeutics and vaccines.
ADVANCED MATERIALS
(2023)
Article
Multidisciplinary Sciences
Thais G. Moreira, Davide Mangani, Laura M. Cox, Jeffrey Leibowitz, Eduardo. L. C. Lobo, Mariana A. Oliveira, Christian D. Gauthier, Brenda N. Nakagaki, Valerie Willocq, Anya Song, Lydia Guo, David C. A. Lima, Gopal Murugaiyan, Oleg Butovsky, Galina Gabriely, Ana C. Anderson, Rafael M. Rezende, Ana Maria C. Faria, Howard L. Weiner
Summary: The dendritic cells (DC) residing in different parts of the gut mucosa, particularly in the upper and lower intestines, exhibit differential PD-L1 and XCR1 expression, driving specific T cell responses to prevent gut inflammation and maintain intestinal homeostasis.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Piriya Luangwattananun, Thanich Sangsuwannukul, Kamonlapat Supimon, Chanitra Thuwajit, Thaweesak Chieochansin, Doonyapat Sa-nguanraksa, Norasate Samarnthai, Pornchai O-Charoenrat, Mutita Junking, Pa-thai Yenchitsomanus
Summary: T cell-based immunotherapy has been revolutionizing cancer treatment. This study demonstrates the potential of alpha PD-L1 x alpha CD3 BATs in treating cancers with positive PD-L1 expression, as BATs showed strong binding ability and anticancer activity against PD-L1-expressing breast cancer cells both in 2D and 3D culture models. Cryopreserved BATs also maintained their binding stability and efficacy.+
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Enrico Munari, Francesca R. Mariotti, Linda Quatrini, Pietro Bertoglio, Nicola Tumino, Paola Vacca, Albino Eccher, Francesco Ciompi, Matteo Brunelli, Guido Martignoni, Giuseppe Bogina, Lorenzo Moretta
Summary: Immune evasion is a crucial strategy adopted by tumor cells to promote survival and metastasis, with PD-1 playing a major role in inhibiting immune responses. Targeting the PD-1/PD-L1 axis has been a significant breakthrough in cancer treatment, representing unprecedented success in various cancer types. Further research on mechanisms regulating PD-1 expression and signaling in tumors is needed to improve therapeutic efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Biomedical
Ramesh Duwa, Ram Hari Pokhrel, Asmita Banstola, Mahesh Pandit, Prakash Shrestha, Jee-Heon Jeong, Jae-Hoon Chang, Simmyung Yook
Summary: Bispecific nanoparticles enhance T cell cytotoxicity by targeting tumor-specific proteins and activating T cells to lyse tumor cells. The nanoparticles also activate dendritic cells and enhance T cell activation, leading to the inhibition of PD-L1 expressed cancer cells. In vivo experiments show that the nanoparticles significantly inhibit tumor growth and enhance intratumoral infiltration of CD4+ and CD8+ T cells, as well as tumor-infiltrated cytokines.
Article
Oncology
Malgorzata Bajor, Agnieszka Graczyk-Jarzynka, Katsiaryna Marhelava, Anna Burdzinska, Angelika Muchowicz, Agnieszka Goral, Andriy Zhylko, Karolina Soroczynska, Kuba Retecki, Marta Krawczyk, Marta Klopotowska, Zofia Pilch, Leszek Paczek, Karl-Johan Malmberg, Sebastien Walchli, Magdalena Winiarska, Radoslaw Zagozdzon
Summary: This study provides new information on the efficacy of PD-L1-targeted CAR against PD-L1(low) targets. The results show that PD-L1-CAR cells have strong reactivity and cytotoxicity against both PD-L1(high) and PD-L1(low) target cells. Additionally, PD-L1-CAR cells also exhibit potent cytotoxic effects against non-malignant cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
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
Biochemistry & Molecular Biology
Ana Bocanegra, Gonzalo Fernandez-Hinojal, Daniel Ajona, Ester Blanco, Miren Zuazo, Maider Garnica, Luisa Chocarro, Elvira Alfaro-Arnedo, Sergio Pineiro-Hermida, Pilar Morente, Leticia Fernandez, Ana Remirez, Miriam Echaide, Maite Martinez-Aguillo, Idoia Morilla, Beatriz Tavira, Alejandra Roncero, Carolina Gotera, Alfonso Ventura, Nerea Recalde, Jose G. Pichel, Juan Jose Lasarte, Luis Montuenga, Ruth Vera, Ruben Pio, David Escors, Grazyna Kochan
Summary: Recent studies show that baseline functional immunity is crucial for the success of immune checkpoint blockade therapies. In this study, high-dimensional systemic immune profiling was performed on non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders had a higher diversity of myeloid phenotypes in their peripheral blood. A diversity index was defined as a potential biomarker of response. Fractalkine (FKN), a chemokine linked to immune chemotaxis and adhesion, was identified as a biomarker of response and correlated with myeloid cell diversity. FKN inhibited lung adenocarcinoma growth in both human and mouse models through the involvement of systemic effector NK cells and increased tumor immune infiltration. FKN also sensitized mouse lung cancer models resistant to anti-PD-1 treatment to immunotherapy, indicating its potential therapeutic use in combination with immunotherapy.
Review
Biochemistry & Molecular Biology
Christian Sordo-Bahamonde, Seila Lorenzo-Herrero, Rocio Granda-Diaz, Alejandra Martinez-Perez, Candelaria Aguilar-Garcia, Juan P. Rodrigo, Juana M. Garcia-Pedrero, Segundo Gonzalez
Summary: The introduction of monoclonal antibodies targeting immune checkpoints has greatly impacted cancer treatment. However, limited overall responses and the lack of predictive biomarkers for patient response are major challenges in immunotherapy. Therefore, it is important to identify novel targets for immunotherapy to expand the range of strategies and improve therapeutic efficacy for cancer patients.
Article
Chemistry, Multidisciplinary
Kelsey L. Swingle, Margaret M. Billingsley, Sourav K. Bose, Brandon White, Rohan Palanki, Apeksha Dave, Savan K. Patel, Ningqiang Gong, Alex G. Hamilton, Mohamad-Gabriel Alameh, Drew Weissman, William H. Peranteau, Michael J. Mitchell
Summary: In utero treatment of congenital disorders using mRNA delivery is a promising strategy to minimize disease burden before irreversible disease onset. LNP stability in amniotic fluid is crucial for efficient intra-amniotic mRNA delivery and potential treatment of congenital disorders prenatally.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Biochemistry & Molecular Biology
David Escors, Ana Bocanegra, Luisa Chocarro, Ester Blanco, Sergio Pineiro-Hermida, Maider Garnica, Leticia Fernandez-Rubio, Ruth Vera, Hugo Arasanz, Grazyna Kochan
Summary: PD-L1/PD-1 blockade immunotherapy has revolutionized cancer treatment, but its mechanisms and effectiveness are still not fully understood. This article reviews the evidence supporting the role of CD4 T cells in anti-tumor immunity and their potential as predictors of response to PD-L1/PD-1 blockade immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Julie Niogret, Helene Berger, Cedric Rebe, Romain Mary, Elise Ballot, Caroline Truntzer, Marion Thibaudin, Valentin Derangere, Christophe Hibos, Lea Hampe, David Rageot, Theo Accogli, Philippe Joubert, Bertrand Routy, James Harker, Frederique Vegran, Francois Ghiringhelli, Fanny Chalmin
Summary: Tfh cells play an important role in antitumor immune response, especially in a CD8(+)-dependent manner, by producing interleukin-21 to support the function of exhausted T cells. Their accumulation in tumor sites and draining lymph nodes is closely associated with treatment efficacy and patient survival.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Joseph S. Dolina, Sylvia Cechova, Christine K. Rudy, Sun-Sang J. Sung, William W. Tang, Joey Lee, Young S. Hahn, Thu H. Le
JOURNAL OF IMMUNOLOGY
(2017)
Article
Gastroenterology & Hepatology
Joseph S. Dolina, Thomas J. Braciale, Young S. Hahn
Article
Immunology
Matthew G. Lassen, John R. Lukens, Joseph S. Dolina, Michael G. Brown, Young S. Hahn
JOURNAL OF IMMUNOLOGY
(2010)
Article
Multidisciplinary Sciences
John R. Lukens, Joseph S. Dolina, Taeg S. Kim, Robert S. Tacke, Young S. Hahn
Article
Immunology
Ana L. Chiodetti, Maria F. Sanchez Vallecillo, Joseph S. Dolina, Maria I. Crespo, Constanza Marin, Stephen P. Schoenberger, Daniel A. Allemandi, Santiago D. Palma, Maria C. Pistoresi-Palencia, Gabriel Moron, Belkys A. Maletto
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Cell Biology
Joseph S. Dolina, Joey Lee, Ryan Q. Griswold, Lara Labarta-Bajo, Sumetha Kannan, Jason A. Greenbaum, Nawal Bahia El Idrissi, Margot J. Pont, Michael Croft, Stephen P. Schoenberger
Review
Immunology
Joseph S. Dolina, Natalija Van Braeckel-Budimir, Graham D. Thomas, Shahram Salek-Ardakani
Summary: Recent research has revealed the heterogeneity within the exhausted CD8(+) T cell lineage, which consists of multiple interconnected subpopulations with distinct characteristics and locations. This understanding calls for a re-focusing of cancer immunotherapies on targeting the driver mechanisms underlying CD8(+) T(ex) development to stabilize functional subsets.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Natalija Budimir, Graham D. Thomas, Joseph S. Dolina, Shahram Salek-Ardakani
Summary: Anti-PD-1/PD-L1 immune checkpoint blockade therapy has revolutionized cancer treatment, but recent studies have revealed the complexity and heterogeneity of CD8 +/- T cell populations in the tumor microenvironment. These studies have also found that CD8 +/- T cell states within and outside the tumor microenvironment have different capacities to respond to immunotherapy.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Natalija Van Braeckel-Budimir, Joseph Samuel Dolina, Jie Wei, Xiao Wang, Shih-Hsun Chen, Pamela Santiago, Guanghuan Tu, Luca Micci, Amir A. Al-Khami, Sophia Pfister, Sripad Ram, Purnima Sundar, Graham Thomas, Hua Long, Wenjing Yang, Shobha Potluri, Shahram Salek-Ardakani
Summary: Our study identified distinct CD8(+) T cell subtypes with functional and migratory signatures that predict tumor rejection upon treatment, with OX40/4-1BB agonism expanding a stem-like T cell subpopulation. PD-(L)1 blockade synergized with OX40/4-1BB costimulation by enhancing the presence of stem-like TILs via a CXCR3-dependent mechanism, providing new insights into combinatorial immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Joseph S. Dolina, Joey Lee, Eugene L. Moore, Jennifer L. Hope, Donald T. Gracias, Takaji Matsutani, Ashu Chawla, Jason A. Greenbaum, Joel Linden, Stephen P. Schoenberger
Summary: During acute infection, CD4(+) regulatory T cells play a crucial role in regulating the immune response by suppressing cytotoxic CD8(+) T lymphocytes through different mechanisms. Early T cells inhibit primary CTL expansion through adenosine production, while late-phase T-regs suppress T cell proliferation through the transfer of cAMP. This study reveals the distinct roles of different T-reg lineages in fine-tuning CTL priming and contraction phases during acute infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)