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45 results on '"Martin, Paul J."'

15. Chronic graft-versus-host-disease treatment in Brazil: analyses of failure-free survival

Author

Vigorito, Afonso Celso, Miranda, Eliana Cristina Martins, Colturato, Vergilio Antonio Rensi, Funke, Vaneuza Araujo Moreira, Fatobene, Giancarlo, Mariano, Livia, Macedo, Maria Cristina Martins de Almeida, Ribeiro, Lorena Bedotti, Daudt, Liane Esteves, Moreira, Maria Cláudia Rodrigues, Bonfim, Carmem, Colella, Marcos Paulo, Seber, Adriana, Rodrigues, Morgani, Duarte, Fernando Barroso, Martin, Paul J., and Flowers, Mary E.D.

Published
2023
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16. Prospective Phase II Trial of Montelukast to Treat Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation and Investigation into Bronchiolitis Obliterans Syndrome Pathogenesis

Author

Williams, Kirsten M., Pavletic, Steven Z., Lee, Stephanie J., Martin, Paul J., Farthing, Don E., Hakim, Frances T., Rose, Jeremy, Manning-Geist, Beryl L., Gea-Banacloche, Juan C., Comis, Leora E., Cowen, Edward W., Justus, David G., Baird, Kristin, Cheng, Guang-Shing, Avila, Daniele, Steinberg, Seth M., Mitchell, Sandra A., and Gress, Ronald E.

Published
2022
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17. Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD

Author

Buxbaum, Nataliya P., primary, Socié, Gerard, additional, Hill, Geoffrey R., additional, MacDonald, Kelli P. A., additional, Tkachev, Victor, additional, Teshima, Takanori, additional, Lee, Stephanie J., additional, Ritz, Jerome, additional, Sarantopoulos, Stefanie, additional, Luznik, Leo, additional, Zeng, Defu, additional, Paczesny, Sophie, additional, Martin, Paul J., additional, Pavletic, Steven Z., additional, Schultz, Kirk R., additional, and Blazar, Bruce R., additional

Published
2023
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18. Donor T cell STAT3 deficiency enables tissue PD-L1–dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity

Author

Li, Qinjian, primary, Wang, Xiaoqi, additional, Song, Qingxiao, additional, Yang, Shijie, additional, Wu, Xiwei, additional, Yang, Dongyun, additional, Marié, Isabelle J., additional, Qin, Hanjun, additional, Zheng, Moqian, additional, Nasri, Ubaydah, additional, Kong, Xiaohui, additional, Wang, Bixin, additional, Lizhar, Elizabeth, additional, Cassady, Kaniel, additional, Tompkins, Josh, additional, Levy, David, additional, Martin, Paul J., additional, Zhang, Xi, additional, and Zeng, Defu, additional

Published
2023
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20. Blockade of trans PD-L1 interaction with CD80 augments antitumor immunity

Author

Zhang, Yuankun, primary, Song, Qingxiao, additional, Cassady, Kaniel, additional, Lee, Michael, additional, Tang, Haidong, additional, Zheng, Moqian, additional, Wang, Bixin, additional, Schones, Dustin E., additional, Fu, Yang-Xin, additional, Riggs, Arthur D., additional, Martin, Paul J., additional, Feng, Ru, additional, and Zeng, Defu, additional

Published
2023
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21. Prognostic Value of Cutaneous Disease Severity Estimates on Survival Outcomes in Patients With Chronic Graft-vs-Host Disease

Author

Baumrin, Emily, primary, Baker, Laura X., additional, Byrne, Michael, additional, Martin, Paul J., additional, Flowers, Mary E., additional, Onstad, Lynn, additional, El Jurdi, Najla, additional, Chen, Heidi, additional, Beeghly-Fadiel, Alicia, additional, Lee, Stephanie J., additional, and Tkaczyk, Eric R., additional

Published
2023
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22. supplemental figure legend from A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation

Author

Arai, Sally, primary, Pidala, Joseph, primary, Pusic, Iskra, primary, Chai, Xiaoyu, primary, Jaglowski, Samantha, primary, Khera, Nandita, primary, Palmer, Jeanne, primary, Chen, George L., primary, Jagasia, Madan H., primary, Mayer, Sebastian A., primary, Wood, William A., primary, Green, Michael, primary, Hyun, Teresa S., primary, Inamoto, Yoshihiro, primary, Storer, Barry E., primary, Miklos, David B., primary, Shulman, Howard M., primary, Martin, Paul J., primary, Sarantopoulos, Stefanie, primary, Lee, Stephanie J., primary, and Flowers, Mary E.D., primary

Published
2023
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24. Targeting Intestinal Epithelial Ceacam1 Expands Peripheral Tregs and Prevents Steroid-Refractory Acute Gut Graft-Versus-Host Disease

Author

Song, Qingxiao, primary, Zheng, Moqian, additional, Li, Qinjian, additional, Wu, Xiwei, additional, Qin, Hanjun, additional, Kang, Tae Hyuk, additional, Hong, Yaqun, additional, Wang, Bixin, additional, Kujawski, Maciej, additional, Shively, Jack, additional, Nakamura, Ryotaro, additional, Martin, Paul J, additional, and Zeng, Defu, additional

Published
2022
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25. Neihulizumab (ALTB-168) in Patients with Steroid-Refractory Acute Graft-Versus-Host-Disease (SR-aGVHD) or Treatment-Refractory Acute Graft-Versus-Host-Disease (TR-aGVHD)

Author

Abedin, Sameem, primary, Hamadani, Mehdi, additional, Holtan, Shernan G, additional, Schiller, Gary J., additional, Gallogly, Molly, additional, Waller, Edmund K., additional, Kosuri, Satyajit, additional, Abhyankar, Sunil H, additional, Anand, Sarah M., additional, Gooptu, Mahasweta, additional, Cho, Iming, additional, Reed, Simona, additional, Lin, Shih-Yao, additional, Hall, Jesse W, additional, and Martin, Paul J, additional

Published
2022
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27. Blockade of trans PD-L1 interaction with CD80 augments antitumor immunity.

Author

Yuankun Zhang, Qingxiao Song, Kaniel Cassady, Lee, Michael, Haidong Tang, Moqian Zheng, Bixin Wang, Schones, Dustin E., Yang-Xin Fu, Riggs, Arthur D., Martin, Paul J., Ru Feng, and Defu Zeng

Subjects
PROGRAMMED death-ligand 1, CD80 antigen, PROGRAMMED cell death 1 receptors, IMMUNITY, CELLULAR immunity
Abstract

PD-L1 has two receptors: PD-1 and CD80. Previous reports assumed that PD-L1 and CD80 interacted in trans, but recent reports showed that only cis PD-L1/CD80 interactions existed, and prevention of cis PD-L1/CD80 interactions on antigen-presenting cells (APCs) reduced antitumor immunity via augmenting PD-L1/PD-1 and CD80/ CTLA4 interactions between T and APCs. Here, using tumor-bearing mice capable of cis and trans or trans only PD-L1/CD80 interactions, we show that trans PD-L1/CD80 interactions do exist between tumor and T cells, and the effects of trans PD-L1/CD80 interactions require tumor cell expression of MHC-I and T cell expression of CD28. The blockade of PD-L1/CD80 interactions in mice with both cis and trans interactions or with only trans interactions augments antitumor immunity by expanding IFN-γ–producing CD8+ T cells and IFN-γ–dependent NOS2-expressing tumor-associated macrophages. Our studies indicate that although cis and trans PD-L1/CD80 interactions may have opposite effects on antitumor immunity, the net effect of blocking PD-L1/CD80 interactions in vivo augments CD8+ T cell-mediated antitumor immunity. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease

Author

Bleakley, Marie, primary, Sehgal, Alison, additional, Seropian, Stuart, additional, Biernacki, Melinda A., additional, Krakow, Elizabeth F., additional, Dahlberg, Ann, additional, Persinger, Heather, additional, Hilzinger, Barbara, additional, Martin, Paul J., additional, Carpenter, Paul A., additional, Flowers, Mary E., additional, Voutsinas, Jenna, additional, Gooley, Theodore A., additional, Loeb, Keith, additional, Wood, Brent L., additional, Heimfeld, Shelly, additional, Riddell, Stanley R., additional, and Shlomchik, Warren D., additional

Published
2022
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32. Rare Variant Genetic Association Study for Transplant-Associated Thrombotic Microangiopathy (TA-TMA) Via Whole Exome Sequencing

Author

Zhang, Zhihui, primary, Wu, Qian Vicky, additional, Amos, Christopher I, additional, Liu, Yanhong, additional, Wei, Hong, additional, Cheng, Chao, additional, Tsavachidis, Spiridon, additional, Bryce, Angela, additional, Sartain, Sarah E, additional, Martinez, Caridad A., additional, Afshar-Kharghan, Vahid, additional, Dong, Jing-fei, additional, Bhatraju, Pavan, additional, Martin, Paul J, additional, Lee, Stephanie J., additional, Makar, Robert S., additional, Bendapudi, Pavan K., additional, and Li, Ang, additional

Published
2021
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33. Long-term survival with mixed chimerism in patients with AML and MDS transplanted after conditioning with targeted busulfan, fludarabine, and thymoglobulin

Author

Yeh, Albert C., primary, O’Donnell, Paul V., additional, Schoch, Gary, additional, Martin, Paul J., additional, McFarland, Chris, additional, McCune, Jeannine S., additional, Cooper, Jason P., additional, Doney, Kris, additional, Flowers, Mary E. D., additional, Sorror, Mohamed L., additional, Appelbaum, Frederick R., additional, Storer, Barry E., additional, Gooley, Ted, additional, and Deeg, H. Joachim, additional

Published
2021
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36. 20. Risk Factors for Breakthrough Cytomegalovirus (CMV) Infection and De Novo Resistance in Hematopoietic Cell Transplantation (HCT) Recipients Receiving Letermovir Prophylaxis

Author

Zamora, Danniel, primary, Perchetti, Garrett, additional, Biernacki, Melinda, additional, Xie, Hu, additional, Castor, Jared L, additional, Joncas-schronce, Laurel, additional, Blazevic, Rachel, additional, Leisenring, Wendy, additional, Huang, Meei-Li, additional, Jerome, Keith, additional, Martin, Paul J, additional, Boeckh, Michael, additional, and Greninger, Alexander L, additional

Published
2021
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41. NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. The 2014 Pathology Working Group Report

Author

Shulman, Howard M., Cardona, Diana M., Greenson, Joel K., Hingorani, Sangeeta, Horn, Thomas, Huber, Elisabeth, Kreft, Andreas, Longerich, Thomas, Morton, Thomas, Myerson, David, Prieto, Victor G., Rosenberg, Avi, Treister, Nathaniel, Washington, Kay, Ziemer, Mirjana, Pavletic, Steven Z., Lee, Stephanie J., Flowers, Mary E.D., Schultz, Kirk R., Jagasia, Madan, Martin, Paul J., Vogelsang, Georgia B., and Kleiner, David E.

Abstract

The 2005 National Institute of Health (NIH) Consensus Conference outlined histopathological diagnostic criteria for the major organ systems affected by both acute and chronic graft-versus-host disease (GVHD). The 2014 Consensus Conference led to this updated document with new information from histopathological studies of GVHD in the gut, liver, skin, and oral mucosa and an expanded discussion of GVHD in the lungs and kidneys. The recommendations for final histological diagnostic categories have been simplified from 4 categories to 3: no GVHD, possible GVHD, and likely GVHD, based on better reproducibility achieved by combining the previous categories of “consistent with GVHD” and “definite GVHD” into the single category of “likely GVHD.” Issues remain in the histopathological characterization of GVHD, particularly with respect to the threshold of histological changes required for diagnostic certainty. Guidance is provided for the incorporation of biopsy information into prospective clinical studies of GVHD, particularly with respect to biomarker validation.

Published
2024
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42. ST2/ Rorγt-Dependent Th1/Th2-like CD4 +Trm Cells Mediate Cutaneous Chronic Gvhd

Author

Li, Qinjian, Wang, Xiaoqi, Kong, Xiaohui, Wang, Bixin, Martin, Paul J., Zhang, Xi, and Zeng, Defu

Abstract

•Allogeneic hematopoietic cell transplantation (Allo-HCT) is a curative therapy for relapsed hematological malignances, but the same alloreactive T cells that eliminate malignant cells in the recipient also mediate graft-versus-host disease (GVHD), and in long-term Allo-HCT patients chronic GVHD (cGVHD) remains the major cause of morbidity and mortality. Th subsets (i.e., Th1, Th2, and Th17) have been associated with cGVHD in certain tissues, but the Th subsets involved in cutaneous cGVHD remain undefined. In the current studies, with a murine model of C57BL/6 donor to MHC-matched C3H.SW recipient, we observed that although IFN-γ +Th1 cells were dominant in the gut, liver, and skin during early acute GVHD, the skin showed a marked expansion of IFN-γ +IL-13 +Th1/Th2-like cells 30 days after HCT at the onset of cGVHD, while IFN-γ +IL-13 -Th1 cells remained dominant in the liver and intestines. The cutaneous Th1/Th2-like cells exhibited characteristics of Ly108 -CD69 +tissue resident memory T (Trm) cells. The expansion of cutaneous Th1/Th2-like cells was RORγt and ST2-dependent because T cells from RORγt -/-or ST2 -/-C57BL/6 donors did not show expansion of the cutaneous Th1/Th2-like cells or induce cutaneous cGVHD. These results indicate that 1) IFN-γ +/IL-13 +Th1/Th2-like CD4 +Trm cells likely play a critical role in the pathogenesis of cutaneous cGVHD; 2) the differentiation of IFN-γ +CD4 +Th1 cells into IFN-γ +IL-13 +Th1/Th2-like cells is RORγt and ST2-dependent. The molecular mechanisms that underpin this differentiation pathway are under investigation.

Published
2023
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43. Blockade of PD-L1/CD80 Interactions Augments Function of Activated Donor T Cells Results in Augmenting Gvhd Induced By Donor Naïve CD8 +t Cells and GVL Effect Mediated By Donor Memory CD8 +T Cells

Author

Song, Qingxiao, Zhang, Yuankun, Cassady, Kaniel, Li, Qinjian, Martin, Paul J., and Zeng, Defu

Abstract

Preventing graft-versus-host disease (GVHD) while preserving graft-versus-leukemia/lymphoma (GVL) activity remains an elusive goal for allogeneic hematopoietic cell transplantation (HCT). It was reported by others that while donor naïve CD8 +T cells mediate both GVHD and GVL activity, donor memory CD8 +T cells could mediate GVL activity without GVHD. We recently reported that in vivo specific blockade of PD-L1/CD80 interactions augment tumor immunity mediated by memory CD8 +T cells (Zhang et al: PNAS 2023). In the current studies, we evaluated the impact of blockade of PD-L1/CD80 on GVHD induced by donor naïve CD8 +T cells and GVL activity-mediated by donor memory CD8 +T cells. Sorted naïve CD8 +T or memory CD8 +T cells and TCD-BM cells from C57BL/6 donors were transplanted into lethal TBI-conditioned BALB/c recipients with or without bearing ALL cancer cells. 4 days after HCT, the recipients were injected I.P. with anti-PD-L1 mAb (43H12) that specifically blocks PD-L1/CD80 interactions without inferring PD-L1/PD-1 interactions or control IgG. We observed that naïve but not memory CD8 +T cells severely infiltrated GVHD target tissues, and the memory CD8 +T cells expanded mainly in the lymphoid tissues. In vivo blockade of PD-L1/CD80 interactions augmented GVHD induced by the naïve T cells and GVL activity mediated by the memory CD8 +T cells. In addition, blockade of PD-L1/CD80 interactions increased production of granzyme B and inflammatory cytokines (IFN-g and TNF-α) of activated donor CD8 +T cells. Since cytolytic activity of effector CD8 +T cell is reported to be associated with its metabolic fitness, we evaluated the effect of blockade PD-L1/CD80 interactions on metabolism of alloreactive donor CD8 +T cells. And blockade of the interactions enhanced the fitness of mitochondria, as indicated by electronic microscopy analysis. The blockade also increased ECAR, OCR, and ATP production of the activated CD8 +T cells, with increased influx of glucose and fatty acids; and the blockade augmented mitophagy of the activated CD8 +T cells, as indicated by reducing mitochondria mass and dysfunctional mitochondria in the CD8 +T cells. The results indicate that 1) PD-L1/CD80 interactions play an important role in regulating the mitochondria function of activated alloreactive CD8 +T cells; 2) Blockade of PD-L1/CD80 interactions can augment GVL activity mediated by donor memory T cells without augmenting GVHD. This is different from blockade of PD-L1/PD-1 interactions that resulted in lethal GVHD.

Published
2023
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44. Donor T cell STAT3 deficiency enables tissue PD-L1– dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.

Author

Qinjian Li, Xiaoqi Wang, Qingxiao Song, Shijie Yang, Xiwei Wu, Dongyun Yang, Marié, Isabelle J., Hanjun Qin, Moqian Zheng, Nasri, Ubaydah, Xiaohui Kong, Bixin Wang, Lizhar, Elizabeth, Cassady, Kaniel, Tompkins, Josh, Levy, David, Martin, Paul J., Xi Zhang, and Defu Zeng

Abstract

STAT3 deficiency (STAT3–/–) in donor T cells prevents graft-versus-host disease (GVHD), but the impact on graft-versusleukemia (GVL) activity and mechanisms of GVHD prevention remains unclear. Here, using murine models of GVHD, we show that STAT3–/– donor T cells induced only mild reversible acute GVHD while preserving GVL effects against nonsusceptible acute lymphoblastic leukemia (ALL) cells in a donor T cell dose–dependent manner. GVHD prevention depended on programmed death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) signaling. In GVHD target tissues, STAT3 deficiency amplified PD-L1/PD-1 inhibition of glutathione (GSH)/Myc pathways that regulate metabolic reprogramming in activated T cells, with decreased glycolytic and mitochondrial ATP production and increased mitochondrial ROS production and dysfunction, leading to tissue-specific deletion of host-reactive T cells and prevention of GVHD. Mitochondrial STAT3 deficiency alone did not reduce GSH expression or prevent GVHD. In lymphoid tissues, the lack of host-tissue PD-L1 interaction with PD-1 reduced the inhibition of the GSH/Myc pathway despite reduced GSH production caused by STAT3 deficiency and allowed donor T cell functions that mediate GVL activity. Therefore, STAT3 deficiency in donor T cells augments PD-1 signaling–mediated inhibition of GSH/Myc pathways and augments dysfunction of T cells in GVHD target tissues while sparing T cells in lymphoid tissues, leading to prevention of GVHD while preserving GVL effects. [ABSTRACT FROM AUTHOR]

Published
2023
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45. Durable discontinuation of systemic therapy in patients affected by chronic graft- versus -host disease.

Author

Chen GL, Onstad L, Martin PJ, Carpenter P, Pidala J, Arai S, Cutler C, Hamilton BK, Lee SJ, and Arora M

Subjects
Humans, Transplantation, Homologous adverse effects, Tissue Donors, Transplantation Conditioning adverse effects, Graft vs Host Disease diagnosis, Graft vs Host Disease drug therapy, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Bronchiolitis Obliterans Syndrome
Abstract

Successful treatment of chronic graft-versus-host disease (GvHD) often requires long-term systemic therapy (ST). Durable discontinuation of ST reflects the resolution of active chronic GvHD. We evaluated the factors associated with durable ST discontinuation, defined as cessation of all ST for ≥12 months, using data from two prospectively followed cohorts from the Chronic GvHD Consortium (n=684). Transplant sources were peripheral blood (89%), bone marrow (6.6%), and cord blood (4.4%) from HLA matched related (37.6%), HLA matched unrelated (45%), and other donor types (18%). Half of the patients received non-myeloablative conditioning. The median time from transplantation to chronic GvHD diagnosis was 7.7 months (range, 1.0-141.3) and the median time from chronic GvHD onset to enrollment into the cohorts was 0.9 months (range, 0.0-12.0). The cumulative incidence estimate of durable ST discontinuation was 32% (95% confidence interval: 28%-37%) at 10 years after enrollment into the cohort. Among patients who discontinued ST, the median time from chronic GvHD diagnosis to durable ST discontinuation was 3.6 years (range, 1.2-10.5). In multivariate analysis, patients who received myeloablative conditioning, had chronic GvHD manifested as moderate/severe lower gastrointestinal involvement, and had a higher (worse) Lee symptom overall score were less likely to attain durable ST discontinuation. In contrast, mild lower gastrointestinal involvement and cord blood (vs. peripheral blood) as the graft source were associated with a greater likelihood of ST discontinuation. Although a minority of patients can discontinue ST permanently, most patients require prolonged ST. Viewing chronic GvHD in this way has implications for management approaches.

Published
2023
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