Human CD26high T cells elicit tumor immunity against multiple malignancies via enhanced migration and persistence

Stefanie R Bailey; Michelle H Nelson; Kinga Majchrzak; Jacob S Bowers; Megan M Wyatt; Aubrey S Smith; Lillian R Neal; Keisuke Shirai; Carmine Carpenito; Carl H June; Michael J Zilliox; Chrystal M Paulos

doi:10.1038/s41467-017-01867-9

Human CD26^high T cells elicit tumor immunity against multiple malignancies via enhanced migration and persistence

Nat Commun. 2017 Dec 6;8(1):1961. doi: 10.1038/s41467-017-01867-9.

Authors

Stefanie R Bailey^{1

2

3}, Michelle H Nelson^{4

5

6

7}, Kinga Majchrzak^{4

5

6

8}, Jacob S Bowers^{4

5

6}, Megan M Wyatt^{4

5

6}, Aubrey S Smith^{4

5

6}, Lillian R Neal^{4

5

6}, Keisuke Shirai^{9

10}, Carmine Carpenito^{11

12}, Carl H June¹¹, Michael J Zilliox¹³, Chrystal M Paulos^{14

15

16}

Affiliations

¹ Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. [email protected].
² Department of Surgery, Medical University of South Carolina, Charleston, SC, 29425, USA. [email protected].
³ Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, SC, 29425, USA. [email protected].
⁴ Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA.
⁵ Department of Surgery, Medical University of South Carolina, Charleston, SC, 29425, USA.
⁶ Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, SC, 29425, USA.
⁷ Aptevo Therapeutics, Seattle, WA, 98121, USA.
⁸ Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, 02-787, Poland.
⁹ Hematology/Oncology Division, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA.
¹⁰ Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, 02714, USA.
¹¹ Department of Pathology and Laboratory Medicine, University of Pennsylvania Cancer Center, Philadelphia, PA, 19104, USA.
¹² Eli Lilly and Company, New York, NY, 10016, USA.
¹³ Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 60153, USA.
¹⁴ Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. [email protected].
¹⁵ Department of Surgery, Medical University of South Carolina, Charleston, SC, 29425, USA. [email protected].
¹⁶ Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, SC, 29425, USA. [email protected].

Abstract

CD8⁺ T lymphocytes mediate potent immune responses against tumor, but the role of human CD4⁺ T cell subsets in cancer immunotherapy remains ill-defined. Herein, we exhibit that CD26 identifies three T helper subsets with distinct immunological properties in both healthy individuals and cancer patients. Although CD26^neg T cells possess a regulatory phenotype, CD26^int T cells are mainly naive and CD26^high T cells appear terminally differentiated and exhausted. Paradoxically, CD26^high T cells persist in and regress multiple solid tumors following adoptive cell transfer. Further analysis revealed that CD26^high cells have a rich chemokine receptor profile (including CCR2 and CCR5), profound cytotoxicity (Granzyme B and CD107A), resistance to apoptosis (c-KIT and Bcl2), and enhanced stemness (β-catenin and Lef1). These properties license CD26^high T cells with a natural capacity to traffic to, regress and survive in solid tumors. Collectively, these findings identify CD4⁺ T cell subsets with properties critical for improving cancer immunotherapy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adoptive Transfer
Animals
Apoptosis
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / immunology
Cell Movement / immunology
Cytokines / immunology
Dipeptidyl Peptidase 4 / blood
Dipeptidyl Peptidase 4 / immunology*
Dipeptidyl Peptidase 4 / metabolism*
Disease Models, Animal
Granzymes
Humans
Immunity
Immunologic Memory
Immunotherapy
Lymphoid Enhancer-Binding Factor 1
Lysosomal-Associated Membrane Protein 1 / immunology
Melanoma / immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasms / immunology*
Neoplasms / pathology
Proto-Oncogene Proteins c-bcl-2
Proto-Oncogene Proteins c-kit
T-Lymphocyte Subsets / immunology*
T-Lymphocytes, Helper-Inducer / immunology
beta Catenin

Substances

BCL2 protein, human
Cytokines
LEF1 protein, human
Lymphoid Enhancer-Binding Factor 1
Lysosomal-Associated Membrane Protein 1
Proto-Oncogene Proteins c-bcl-2
beta Catenin
Proto-Oncogene Proteins c-kit
DPP4 protein, human
Dipeptidyl Peptidase 4
GZMB protein, human
Granzymes

Abstract

Publication types

MeSH terms

Substances

Grants and funding