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Review ArticleReview Article

Targeting Immune Checkpoints in Hematologic Malignancies

Gheath Alatrash, Naval Daver and Elizabeth A. Mittendorf
Michael G. Rosenblum, ASSOCIATE EDITOR
Pharmacological Reviews October 2016, 68 (4) 1014-1025; DOI: https://doi.org/10.1124/pr.116.012682
Gheath Alatrash
Departments of Stem Cell Transplantation and Cellular Therapy (G.A., E.A.M.), Leukemia (N.D.), and Breast Surgical (E.A.M.) Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Naval Daver
Departments of Stem Cell Transplantation and Cellular Therapy (G.A., E.A.M.), Leukemia (N.D.), and Breast Surgical (E.A.M.) Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Elizabeth A. Mittendorf
Departments of Stem Cell Transplantation and Cellular Therapy (G.A., E.A.M.), Leukemia (N.D.), and Breast Surgical (E.A.M.) Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Michael G. Rosenblum
Departments of Stem Cell Transplantation and Cellular Therapy (G.A., E.A.M.), Leukemia (N.D.), and Breast Surgical (E.A.M.) Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Roles: ASSOCIATE EDITOR
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Abstract

The use of antibodies that target immune checkpoint molecules on the surface of T-lymphocytes and/or tumor cells has revolutionized our approach to cancer therapy. Cytotoxic-T-lymphocyte antigen (CTLA-4) and programmed cell death protein 1 (PD-1) are the two most commonly targeted immune checkpoint molecules. Although the role of antibodies that target CTLA-4 and PD-1 has been established in solid tumor malignancies and Food and Drug Administration approved for melanoma and non-small cell lung cancer, there remains a desperate need to incorporate immune checkpoint inhibition in hematologic malignancies. Unlike solid tumors, a number of considerations must be addressed to appropriately employ immune checkpoint inhibition in hematologic malignancies. For example, hematologic malignancies frequently obliterate the bone marrow and lymph nodes, which are critical immune organs that must be restored for appropriate response to immune checkpoint inhibition. On the other hand, hematologic malignancies are the quintessential immune responsive tumor type, as proven by the success of allogeneic stem cell transplantation (allo-SCT) in hematologic malignancies. Also, sharing an immune cell lineage, malignant hematologic cells often express immune checkpoint molecules that are absent in solid tumor cells, thereby offering direct targets for immune checkpoint inhibition. A number of clinical trials have demonstrated the potential for immune checkpoint inhibition in hematologic malignancies before and after allo-SCT. The ongoing clinical studies and complimentary immune correlatives are providing a growing body of knowledge regarding the role of immune checkpoint inhibition in hematologic malignancies, which will likely become part of the standard of care for hematologic malignancies.

Footnotes

  • G.A. is supported by a grant from the Leukemia & Lymphoma Society. N.D. is supported by grants from the Ladies Leukemia League and the Anderson Cancer Center Leukemia SPORE. E.A.M. is an R. Lee Clark Fellow of the University of Texas Anderson Cancer Center supported by the Jeanne F. Shelby Scholarship Fund.

  • dx.doi.org/10.1124/pr.116.012682.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 68 (4)
Pharmacological Reviews
Vol. 68, Issue 4
1 Oct 2016
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Review ArticleReview Article

Checkpoint Blockade for Hematologic Malignancies

Gheath Alatrash, Naval Daver and Elizabeth A. Mittendorf
Pharmacological Reviews October 1, 2016, 68 (4) 1014-1025; DOI: https://doi.org/10.1124/pr.116.012682

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Review ArticleReview Article

Checkpoint Blockade for Hematologic Malignancies

Gheath Alatrash, Naval Daver and Elizabeth A. Mittendorf
Pharmacological Reviews October 1, 2016, 68 (4) 1014-1025; DOI: https://doi.org/10.1124/pr.116.012682
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  • Article
    • Abstract
    • I. Introduction
    • II. T Cell Inhibitory Pathways: Cytotoxic-T-lymphocyte Antigen 4, Programmed Death Protein 1, and Programmed Death Protein Ligand 1
    • III. Targeting Immune Checkpoint Molecules in Cancer
    • IV. Immune Checkpoint Inhibition in Hematologic Tumors
    • VI. Conclusion and Future Directions
    • Acknowledgments
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