Review
Chemistry, Multidisciplinary
Faezeh Dangkoub, Mojtaba Sankian, Mohsen Tafaghodi, Mahmoud Reza Jaafari, Ali Badiee
Summary: This paper reviews the application of nanocarriers in inducing immunotolerance, with a focus on targeted delivery to APCs and direct targeting of autoreactive lymphocytes. The physicochemical properties and composition of NCs play essential roles in achieving the desired immunological outcome, making them a promising approach for treating autoimmune diseases in humans.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Endocrinology & Metabolism
Terri C. Thayer, Joanne Davies, James A. Pearson, Stephanie J. Hanna, Li Wen, F. Susan Wong
Summary: Our results suggest that a loss of NOD-LNSC MHC-independent suppressive mechanisms may contribute to diabetes development. In contrast, non-MHC-matched, control C57BL/6 mouse LNSC suppressed T-cell receptor engagement by anti-CD3/CD28 via MHC-independent mechanisms, modifying antigen sensitivity and effector function.
Review
Medicine, General & Internal
Naoya Sato, Shigeru Marubashi
Summary: Allogeneic islet transplantation is an effective treatment for Type 1 diabetes, but chronic rejection remains a challenge for long-term engraftment. Breakthroughs in tolerance induction using ADLs show great potential, but obstacles such as islet immunogenicity and instant blood-mediated response need to be addressed in the future.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Martina Damo, Noah I. Hornick, Aarthi Venkat, Ivana William, Kathryn Clulo, Srividhya Venkatesan, Jiaming He, Eric Fagerberg, Jennifer L. Loza, Darwin Kwok, Aya Tal, Jessica Buck, Can Cui, Jaiveer Singh, William E. Damsky, Jonathan S. Leventhal, Smita Krishnaswamy, Nikhil S. Joshi
Summary: The presence of self-reactive T cells in the peripheral T cell repertoire of healthy individuals is influenced by checkpoint receptors like PD-1. However, the high frequency of immune-related adverse events in cancer patients treated with checkpoint inhibitors challenges this model. This study developed a mouse model to demonstrate the role of PD-1 in maintaining tissue tolerance and preventing immunopathology.
Article
Biochemistry & Molecular Biology
Raquel Garcia-Ferreras, Jesus Osuna-Perez, Guillermo Ramirez-Santiago, Almudena Mendez-Perez, Andres M. Acosta-Moreno, Lara Del Campo, Maria J. Gomez-Sanchez, Marta Iborra, Beatriz Herrero-Fernandez, Jose M. Gonzalez-Granado, Francisco Sanchez-Madrid, Yolanda R. Carrasco, Patricia Boya, Nuria Martinez-Martin, Esteban Veiga
Summary: Research shows that B cells capture bacteria from infected dendritic cells through trans-phagocytosis, and this process activates CD8(+) T cells to regulate bacterial infections. Additionally, it is demonstrated that B cells that have captured bacteria expressing tumor antigens may be utilized as novel cellular immunotherapies against cancer.
Review
Immunology
Sung-Woo Lee, Gil-Woo Lee, Hee-Ok Kim, Jae-Ho Cho
Summary: Immune diversification is important for host protection against pathogens. CD8(+) T cells play a crucial role in inhibiting pathogen spread and disease development by inducing apoptosis in infected host cells. Many studies have revealed the mechanisms of CD8(+) T cell activation, proliferation, and differentiation. This review focuses on the heterogeneity of naive CD8(+) T cells and its contribution to the antigen-specific CD8(+) T cell response.
Article
Oncology
Nikola Cousin, Stefan Cap, Manuel Dihr, Carlotta Tacconi, Michael Detmar, Lothar C. Dieterich
Summary: A new study using a lymphatic-specific PD-L1 knockout mouse model reveals that lymphatic endothelial PD-L1 expression reduces tumor immunity by inducing apoptosis in tumor-specific CD8(+) central memory cells in tumor-draining lymph nodes.
Article
Cell Biology
Yutong Wu, Hongbo Ai, Yuhang Xi, Jiulin Tan, Ying Qu, Jianzhong Xu, Fei Luo, Ce Dou
Summary: The bone microenvironment plays a role in promoting cancer cell proliferation and dissemination through apoptotic bodies (ABs) produced by osteoclasts. In this study, it was discovered that AB-null mice showed resistance to breast cancer cell implantation, with increased CD8+ T cell infiltrations and higher survival rate. The researchers found that membranous Siglec15 on osteoclast-derived ABs binds with sialylated Toll-like receptor 2 (TLR2) and inhibits activation of naive CD8+ T cells. Furthermore, treatment with Siglec15 neutralizing antibodies decreased secondary metastases and improved the survival rate in mice with advanced breast cancer bone metastasis. These findings reveal the immunosuppressive function of osteoclast-derived ABs in the bone-tumor niche and highlight the potential of Siglec15 as a target for anti-resorption and immunotherapy.
CELL REPORTS MEDICINE
(2023)
Article
Immunology
Emma L. Lewis, Rong Xu, Jean-Christophe Beltra, Shin Foong Ngiow, Jordana Cohen, Rahul Telange, Alexander Crane, Deirdre Sawinski, E. John Wherry, Paige M. Porrett
Summary: Studies demonstrate that pregnancy induces exhausted CD8 T cells in mothers, prolonging allograft survival. Maternal CD8 T cells during pregnancy share exhaustion features with CD8 T cells from chronic infection and cancer.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Sayuri Iwai, Aiko Okada, Kei Sasano, Masayuki Endo, Sho Yamazaki, Xin Wang, Takashi Shimbo, Takuji Tomimatsu, Tadashi Kimura, Katsuto Tamai
Summary: The study found that mesenchymal stem/stromal cells (MSCs) transferred by maternal microchimerism have the potential to induce immune tolerance, which can be further enhanced with drug therapy. This research provides insights into immune tolerance induction and paves the way for developing new therapies for autoimmune or genetic diseases using maternally derived cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell Biology
Youhui Si, Yihan Wang, Qiaomu Tian, Qiang Wang, Jared M. Pollard, Pramod K. Srivastava, Aaron P. Esser-Kahn, Joel H. Collier, Anne I. Sperling, Anita S. Chong
Summary: The current study provides evidence that intranasal administration of peptide antigens primes naive CD8+ T cells in the lung independently before priming in the draining mediastinal lymph node. The transcriptional responses of lung cDC1 and cDC2 to intranasal nanofiber immunization were found to be distinct, but both subsets acquire shared transcriptional responses upon migration into the lymph node, revealing a stepwise activation process of cDC1 and cDC2 towards their ability to cross-prime effector and functional memory CD8+ T cell responses.
Article
Biology
Emily N. Truckenbrod, Kristina S. Burrack, Todd P. Knutson, Henrique Borges da Silva, Katharine E. Block, Stephen D. O'Flanagan, Katie R. Stagliano, Arthur A. Hurwitz, Ross B. Fulton, Kristin R. Renkema, Stephen C. Jameson
Summary: The study found that self-specific CD8(+) T cells in a physiological setting exhibit similar phenotypic and gene expression profiles, but show differences in function, such as enhanced self-tolerance in mice lacking Dct. This suggests that predicting CD8(+) T cell self-specificity is challenging based on precursor frequency, phenotype, or initial responsiveness, and that certain gene expression characteristics like reduced activation-induced CD25 expression may help identify functionally tolerant cells.
Article
Immunology
Martina Damo, D. Scott Wilson, Elyse A. Watkins, Jeffrey A. Hubbell
Summary: Hepatocytes play a crucial role in inducing immunologic tolerance in the liver through cross-presentation of extracellular antigens. This study demonstrates that hepatocytes are capable of efficiently inducing cross-tolerance of specific T cells, providing evidence for their potential as valuable candidates for targeted tolerogenic treatments in vivo.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Kazuki Sasaki, Mouhamad Al Moussawy, Khodor Abou-Daya, Camila Macedo, Amira Hosni-Ahmed, Silvia Liu, Mariam Juya, Alan F. Zahorchak, Diana M. Metes, Angus W. Thomson, Fadi G. Lakkis, Hossam A. Abdelsamed
Summary: Activated memory T cells can influence the phenotype and transcription of surrounding naive T cells, which may have implications for immune responses following vaccination, infection, or transplantation.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eunjung Cho, Seongeun Han, Hyeon Seok Eom, Sang-Jin Lee, Chungyong Han, Rohit Singh, Seon-Hee Kim, Bo-Mi Park, Byoung-Gie Kim, Young H. Kim, Byoung S. Kwon, Ki Taek Nam, Beom K. Choi
Summary: The interaction between regulatory T (Treg) cells and self-reactive T cells is crucial for maintaining immune tolerance. This study reveals that self-antigens can activate CD8(+) T cells and induce delayed proliferation of Treg cells. The P53 signaling pathway plays a critical role in this process. Understanding the mechanisms of Treg cell stimulation and its implications in autoimmune diseases and cancer immunotherapy is important.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Valerie K. Conrad, Christopher J. Dubay, Mehrnoush Malek, Ryan R. Brinkman, Yoshinobu Koguchi, William L. Redmond
Article
Oncology
David B. Page, Joanna Pucilowska, Katherine G. Sanchez, Valerie K. Conrad, Alison K. Conlin, Anupama K. Acheson, Kelly S. Perlewitz, James H. Imatani, Shaghayegh Aliabadi-Wahle, Nicole Moxon, Staci L. Mellinger, Amanda Y. Seino, Martiza Martel, Yaping Wu, Zhaoyu Sun, William L. Redmond, Venkatesh Rajamanickam, Dottie Waddell, Deborah Laxague, Monil Shah, Shu-Ching Chang, Walter J. Urba
CLINICAL CANCER RESEARCH
(2020)
Article
Oncology
Joshua M. Walker, Annah S. Rolig, Deborah H. Charych, Ute Hoch, Melissa J. Kasiewicz, Daniel C. Rose, Michael J. McNamara, Ian F. Hilgart-Martiszus, William L. Redmond
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Oncology
Julie N. Graff, Tomasz M. Beer, Joshi J. Alumkal, Rachel E. Slottke, William L. Redmond, George Thomas, Reid F. Thompson, Mary A. Wood, Yoshinobu Koguchi, Yiyi Chen, Emile Latour, Raymond C. Bergan, Charles G. Drake, Amy E. Moran
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Immunology
Mohammad Farhad Amani, Annah S. Rolig, William L. Redmond
JOURNAL OF IMMUNOLOGY
(2020)
Article
Multidisciplinary Sciences
Zhaoyu Sun, Richard Nyberg, Yaping Wu, Brady Bernard, William L. Redmond
Summary: The TSA Opal multiplex immunohistochemistry protocol has been used to characterize immune infiltration in human cancers. Two improved protocols were developed for a 7-color panel with 6 biomarkers, showing that antigen retrieval method is crucial for staining intensity. The study demonstrated the importance of proper antigen retrieval method in multiplex immunohistochemistry and its impact on individual biomarker staining intensity.
Article
Oncology
Dana A. Emerson, Annah S. Rolig, William L. Redmond
Summary: The combination of CTLA-4 blockade and OX40-specific monoclonal antibody has been shown to enhance antitumor immunity by upregulating Eomes expression in CD8(+) T cells. Further modulation of Eomes expression through ITK signaling with ibrutinib can lead to enhanced tumor regression and improved survival, making the combination therapy a potential triple therapy option for improving immunotherapy efficacy.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Immunology
Robin C. Orozco, Kristi Marquardt, Kerri Mowen, Linda A. Sherman
Summary: The proautoimmune allele of PTPN22 promotes a strong antitumor response in innate and adaptive immune cells, leading to enhanced resistance to tumor growth in mice. This results in increased infiltration of CD8 T cells, CD4 T cells, and cDC1 cells in tumors from PEP-619WW mice, indicating superior control of tumors compared to wild type mice. Additionally, tumor-infiltrating cDC1 cells from PEP-619WW mice show decreased PD-L1 expression, further contributing to the antitumor immune response.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Oncology
Yoshinobu Koguchi, Noriko Iwamoto, Takashi Shimada, Shu-Ching Chang, John Cha, Brendan D. Curti, Walter J. Urba, Brian D. Piening, William L. Redmond
Summary: Trough levels of ipilimumab may be a useful biomarker for long-term survival of patients with advanced melanoma, with associations with CXCL11 and sCD25 suggesting a baseline-driven E-R relationship, while associations with CRP and IL-6 levels indicate response-driven E-R relationship.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Brie Chun, Joanna Pucilowska, ShuChing Chang, Isaac Kim, Benjamin Nikitin, Yoshinobu Koguchi, William L. Redmond, Brady Bernard, Venkatesh Rajamanickam, Nathan Polaske, Paul A. Fields, Valerie Conrad, Mark Schmidt, Walter J. Urba, Alison K. Conlin, Heather L. McArthur, David B. Page
Summary: This study investigates the effects of pembrolizumab combined with paclitaxel or capecitabine on T-cell subsets in triple-negative breast cancer patients. The results show that these treatments result in similar lymphodepletions across peripheral T-cell subsets and do not alter T-cell clonal diversity. The findings contribute to our understanding of the impact of chemoimmunotherapy on the immune system.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Rashi Yadav, William L. Redmond
Summary: This review discusses the impact of OX40 agonists on T cell function and the therapeutic potential of OX40 agonists alone or in conjunction with ICB for patients with advanced malignancies.
CURRENT ONCOLOGY REPORTS
(2022)
Article
Oncology
Annah S. Rolig, Daniel C. Rose, Grace Helen McGee, Werner Rubas, Saul Kivimae, William L. Redmond
Summary: This study aims to evaluate whether intratumoral NKTR-262 combined with systemic BEMPEG treatment can improve tumor-specific immunity and survival. The results showed that BEMPEG+NKTR-262 significantly improved survival and inhibited tumor growth by expanding activated CD8(+) T cells and enhancing cytolytic function.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Yoshinobu Koguchi, William L. Redmond
Summary: While immune checkpoint blockade has revolutionized cancer treatment, the majority of patients do not benefit from it. Various efforts have been made to interrogate the immune system using different biospecimens, technologies, and disciplines, but consistent biomarkers of response have remained elusive. Pharmacokinetics studies, however, provide critical information and may reveal useful biomarkers.
IMMUNOLOGICAL INVESTIGATIONS
(2022)
Article
Biochemical Research Methods
Daniel C. Rose, Annah S. Rolig, William L. Redmond
Summary: This article describes a flow cytometry panel specifically designed to assess the expression of activation and exhaustion markers in expanding lymphocyte populations in tumor-bearing mice. It enables the assessment of multiple functional states and immune checkpoint markers across various immune cell subsets in murine whole blood, lymph nodes, and tumor.
Article
Oncology
Elizabeth R. Sturgill, Annah S. Rolig, Stefanie N. Linch, Courtney Mick, Melissa J. Kasiewicz, Zhaoyu Sun, Peter G. Traber, Harold Shlevin, William L. Redmond
Summary: Combining Gal-3 inhibition with aOX40 therapy promotes tumor regression and increases survival by reducing M-MDSC-mediated immune suppression, enhancing CD8(+) T cell recruitment, leading to improved tumor regression and survival.