Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a common treatment for patients with blood-derived cancers, which causes both desirable (graft-versus-tumor) and undesirable (graft-versus-host disease) effects. We have identified a population of CD8+ T cells that can mediate the graft-versus-tumor effect without inducing the potentially devastating side effect of graft-versus-host disease during allogeneic HSCT. In an effort to devise new strategies for improving outcomes of patients undergoing allogeneic HSCT, this project seeks to identify the features of this T cell population that contribute to the separation of these two simultaneously occurring immune responses during allogeneic HSCT.

Public Health Relevance

Allogeneic hematopoietic stem cell transplantation (HSCT) is a common treatment for patients with blood-derived cancers, which causes both desirable (graft-versus-tumor) and undesirable (graft- versus-host disease) effects. We have identified a population of CD8+ T cells that can mediate the graft- versus-tumor effect without inducing the potentially devastating side effect of graft-versus-host disease during allogeneic HSCT. In an effort to devise new strategies for improving outcomes of patients undergoing allogeneic HSCT, this project seeks to identify the features of this T cell population that contribute to the separation of these two simultaneously occurring immune responses during allogeneic HSCT.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI117282-02
Application #
9101993
Study Section
Transplantation, Tolerance, and Tumor Immunology (TTT)
Program Officer
Nabavi, Nasrin N
Project Start
2015-07-01
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Freund-Brown, Jacquelyn; Chirino, Leilani; Kambayashi, Taku (2018) Strategies to enhance NK cell function for the treatment of tumors and infections. Crit Rev Immunol 38:105-130
Freund-Brown, Jacquelyn; Choa, Ruth; Singh, Brenal K et al. (2017) Cutting Edge: Murine NK Cells Degranulate and Retain Cytotoxic Function without Store-Operated Calcium Entry. J Immunol :
Freund, Jacquelyn; May, Rebecca M; Yang, Enjun et al. (2016) Activating Receptor Signals Drive Receptor Diversity in Developing Natural Killer Cells. PLoS Biol 14:e1002526
Leichner, Theresa M; Satake, Atsushi; Kambayashi, Taku (2016) TCR signaling by conventional CD4+ T cells is required for optimal maintenance of peripheral regulatory T cell numbers. Immun Inflamm Dis 4:148-154
Singh, Brenal K; Kambayashi, Taku (2016) The Immunomodulatory Functions of Diacylglycerol Kinase ?. Front Cell Dev Biol 4:96
Yang, Enjun; Singh, Brenal K; Paustian, Amanda M Schmidt et al. (2016) Diacylglycerol Kinase ? Is a Target To Enhance NK Cell Function. J Immunol 197:934-41