Challenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders

doi:10.1186/s40425-016-0201-6

Review

. 2016 Dec 20:4:95.

doi: 10.1186/s40425-016-0201-6. eCollection 2016.

Challenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders

Tycel Phillips¹, Sumana Devata¹, Ryan A Wilcox²

Affiliations

¹ Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI USA.
² Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI USA ; University of Michigan Comprehensive Cancer Center, 4310 Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109 USA.

PMID: 28031823
PMCID: PMC5170899
DOI: 10.1186/s40425-016-0201-6

Review

Challenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders

Tycel Phillips et al. J Immunother Cancer. 2016.

. 2016 Dec 20:4:95.

doi: 10.1186/s40425-016-0201-6. eCollection 2016.

Authors

Tycel Phillips¹, Sumana Devata¹, Ryan A Wilcox²

Affiliations

¹ Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI USA.
² Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI USA ; University of Michigan Comprehensive Cancer Center, 4310 Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109 USA.

PMID: 28031823
PMCID: PMC5170899
DOI: 10.1186/s40425-016-0201-6

Abstract

The T-cell lymphoproliferative disorders are a heterogeneous group of non-Hodgkin's lymphomas (NHL) for which current therapeutic strategies are inadequate, as most patients afflicted with these NHL will succumb to disease progression within 2 years of diagnosis. Appreciation of the genetic and immunologic landscape of these aggressive NHL, including PD-L1 (B7-H1, CD274) expression by malignant T cells and within the tumor microenvironment, provides a strong rationale for therapeutic targeting this immune checkpoint. While further studies are needed, the available data suggests that responses with PD-1 checkpoint blockade alone will unlikely approach those achieved in other lymphoproliferative disorders. Herein, we review the unique challenges posed by the T-cell lymphoproliferative disorders and discuss potential strategies to optimize checkpoint blockade in these T-cell derived malignancies.

Keywords: Checkpoint blockade; Cutaneous T-cell lymphoma; PD-L1; Peripheral T-cell lymphoma.

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References

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[1] Postow MA, Callahan MK, Wolchok JD. Immune Checkpoint Blockade in Cancer Therapy. J Clin Oncol. 2015;33:1974–1982. doi: 10.1200/JCO.2014.59.4358. - DOI - PMC - PubMed

[2] Postow MA, Callahan MK, Wolchok JD. Immune Checkpoint Blockade in Cancer Therapy. J Clin Oncol. 2015;33:1974–1982. doi: 10.1200/JCO.2014.59.4358. - DOI - PMC - PubMed

[3] Scott DW, Gascoyne RD. The tumour microenvironment in B cell lymphomas. Nat Rev Cancer. 2014;14:517–534. doi: 10.1038/nrc3774. - DOI - PubMed

[4] Scott DW, Gascoyne RD. The tumour microenvironment in B cell lymphomas. Nat Rev Cancer. 2014;14:517–534. doi: 10.1038/nrc3774. - DOI - PubMed

[5] Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004;351:2159–2169. doi: 10.1056/NEJMoa041869. - DOI - PubMed

[6] Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004;351:2159–2169. doi: 10.1056/NEJMoa041869. - DOI - PubMed

[7] Georgiou K, Chen L, Berglund M, Ren W, de Miranda NF, Lisboa S, Fangazio M, Zhu S, Hou Y, Wu K, et al. Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas. Blood. 2016;127:3026–3034. doi: 10.1182/blood-2015-12-686550. - DOI - PubMed

[8] Georgiou K, Chen L, Berglund M, Ren W, de Miranda NF, Lisboa S, Fangazio M, Zhu S, Hou Y, Wu K, et al. Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas. Blood. 2016;127:3026–3034. doi: 10.1182/blood-2015-12-686550. - DOI - PubMed

[9] Keane C, Vari F, Hertzberg M, Cao KA, Green MR, Han E, Seymour JF, Hicks RJ, Gill D, Crooks P, et al. Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: a population-based study. Lancet Haematol. 2015;2:e445–e455. doi: 10.1016/S2352-3026(15)00150-7. - DOI - PubMed

[10] Keane C, Vari F, Hertzberg M, Cao KA, Green MR, Han E, Seymour JF, Hicks RJ, Gill D, Crooks P, et al. Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: a population-based study. Lancet Haematol. 2015;2:e445–e455. doi: 10.1016/S2352-3026(15)00150-7. - DOI - PubMed

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Challenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders

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Challenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders

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