IL-15 trans-signaling with the superagonist RLI promotes effector/memory CD8+ T cell responses and enhances antitumor activity of PD-1 antagonists

Journal of Immunology

Volumn 197, Issue 1, 2016, Pages 168-178

  Desbois, Mélanie ^a,b,c,d   Vu, Pauline Le ^a,b   Coutzac, Clélia ^a,b,c   Marcheteau, Elie ^e   Béal, Coralie ^a   Terme, Magali ^e   Gey, Alain ^e   Morisseau, Sébastien ^f,g   Teppaz, Géraldine ^g   Boselli, Lisa ^a,b   Jacques, Yannick ^f   Béchard, David ^g   Tartour, Eric ^e   Cassard, Lydie ^a,b   Chaput, Nathalie ^a,b  

^a INSERM   (France)

^b CNRS   (France)

^c UNIVERSITÉ PARIS SACLAY   (France)

^d Cytune Pharma SAS   (France)

^e PARIS CARDIOVASCULAR RESEARCH CENTER   (France)

^f UNIVERSITÉ DE NANTES   (France)

^g HÔTEL DIEU   (France)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 15; INTERLEUKIN 15 RECEPTOR ALPHA; MUCIN 3; PIDILIZUMAB; PROGRAMMED DEATH 1 RECEPTOR; PROTEIN INHIBITOR; RECEPTOR LINKER INTERLEUKIN 15; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; HYBRID PROTEIN; IL-15RALPHA-SUSHI DOMAIN-LINKER-IL-15 FUSION PROTEIN; MONOCLONAL ANTIBODY; PDCD1 PROTEIN, MOUSE; STAT5 PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER GROWTH; CD8+ T LYMPHOCYTE; COLORECTAL CARCINOMA; CONTROLLED STUDY; EFFECTOR CELL; EX VIVO STUDY; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VIVO STUDY; KIDNEY CARCINOMA; MEMORY T LYMPHOCYTE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; TUMOR ASSOCIATED LEUKOCYTE; ADENOCARCINOMA; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; C57BL MOUSE; CARCINOMA, RENAL CELL; CELL PROLIFERATION; COLONIC NEOPLASMS; COMBINATION DRUG THERAPY; CYTOTOXICITY; DRUG EFFECTS; DRUG POTENTIATION; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; PROCEDURES; TUMOR CELL LINE; TUMOR VOLUME;

ADENOCARCINOMA; ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CARCINOMA, RENAL CELL; CD8-POSITIVE T-LYMPHOCYTES; CELL LINE, TUMOR; CELL PROLIFERATION; COLONIC NEOPLASMS; CYTOTOXICITY, IMMUNOLOGIC; DRUG SYNERGISM; DRUG THERAPY, COMBINATION; HUMANS; IMMUNOLOGIC MEMORY; IMMUNOTHERAPY; INTERLEUKIN-15; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; PROGRAMMED CELL DEATH 1 RECEPTOR; RECOMBINANT FUSION PROTEINS; SIGNAL TRANSDUCTION; STAT5 TRANSCRIPTION FACTOR; TUMOR BURDEN;

EID: 84975299077     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1600019     Document Type: Article

References (40)

1. Mellman, I., G. Coukos, and G. Dranoff. 2011. Cancer immunotherapy comes of age. Nature 480: 480-489.
2. Rosenberg, S. A. 2014. IL-2: The first effective immunotherapy for human cancer. J. Immunol. 192: 5451-5458.
3. Cesana, G. C., G. DeRaffele, S. Cohen, D. Moroziewicz, J. Mitcham, J. Stoutenburg, K. Cheung, C. Hesdorffer, S. Kim-Schulze, and H. L. Kaufman. 2006. Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J. Clin. Oncol. 24: 1169-1177.
4. Waldmann, T. A. 2006. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat. Rev. Immunol. 6: 595-601.
5. Mattei, F., G. Schiavoni, F. Belardelli, and D. F. Tough. 2001. IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded RNA, or lipopolysaccharide and promotes dendritic cell activation. J. Immunol. 167: 1179-1187.
6. Rubinstein, M. P., A. N. Kadima, M. L. Salem, C. L. Nguyen, W. E. Gillanders, and D. J. Cole. 2002. Systemic administration of IL-15 augments the antigenspecific primary CD8+ T cell response following vaccination with peptidepulsed dendritic cells. J. Immunol. 169: 4928-4935.
7. Dubois, S., J. Mariner, T. A. Waldmann, and Y. Tagaya. 2002. IL-15Ralpha recycles and presents IL-15 in trans to neighboring cells. Immunity 17: 537-547.
8. Mortier, E., A. Quéméner, P. Vusio, I. Lorenzen, Y. Boublik, J. Grötzinger, A. Plet, and Y. Jacques. 2006. Soluble interleukin-15 receptor alpha (IL-15R alpha)-sushi as a selective and potent agonist of IL-15 action through IL-15R beta/gamma: hyperagonist IL-15 x IL-15R alpha fusion proteins. J. Biol. Chem. 281: 1612-1619.
9. Bouchaud, G., L. Garrigue-Antar, V. Solé, A. Quéméner, Y. Boublik, E. Mortier, H. Perdreau, Y. Jacques, and A. Plet. 2008. The exon-3-encoded domain of IL-15ralpha contributes to IL-15 high-affinity binding and is crucial for the IL-15 antagonistic effect of soluble IL-15Ralpha. J. Mol. Biol. 382: 1-12.
10. Bessard, A., V. Solé, G. Bouchaud, A. Quéméner, and Y. Jacques. 2009. High antitumor activity of RLI, an interleukin-15 (IL-15)-IL-15 receptor alpha fusion protein, in metastatic melanoma and colorectal cancer. Mol. Cancer Ther. 8: 2736-2745.
11. Vincent, M., A. Bessard, D. Cochonneau, G. Teppaz, V. Sole, M. Maillasson, S. Birkle, L. Garrigue-Antar, A. Quemener, and Y. Jacques. 2013. Tumor targeting of the IL-15 superagonist RLI by an anti-GD2 antibody strongly enhances its antitumor potency. Int. J. Cancer 133: 757-765.
12. Vincent, M., G. Teppaz, L. Lajoie, V. Solé, A. Bessard, M. Maillasson, S. Loisel, D. Béchard, B. Clémenceau, G. Thibault, et al. 2014. Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse. MAbs 6: 1026-1037.
13. Badoual, C., S. Hans, N. Merillon, C. Van Ryswick, P. Ravel, N. Benhamouda, E. Levionnois, M. Nizard, A. Si-Mohamed, N. Besnier, et al. 2013. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res. 73: 128-138.
14. Sánchez-Paulete, A. R., F. J. Cueto, M. Martínez-López, S. Labiano, A. Morales-Kastresana, M. E. Rodríguez-Ruiz, M. Jure-Kunkel, A. Azpilikueta, M. A. Aznar, J. I. Quetglas, et al. 2016. Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov. 6: 71-79.
15. Gubin, M. M., X. Zhang, H. Schuster, E. Caron, J. P. Ward, T. Noguchi, Y. Ivanova, J. Hundal, C. D. Arthur, W. J. Krebber, et al. 2014. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 515: 577-581.
16. Matsushita, H., M. D. Vesely, D. C. Koboldt, C. G. Rickert, R. Uppaluri, V. J. Magrini, C. D. Arthur, J. M. White, Y. S. Chen, L. K. Shea, et al. 2012. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 482: 400-404.
17. Hannani, D., M. Vétizou, D. Enot, S. Rusakiewicz, N. Chaput, D. Klatzmann, M. Desbois, N. Jacquelot, N. Vimond, S. Chouaib, et al. 2015. Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25. Cell Res. 25: 208-224.
18. Sakuishi, K., L. Apetoh, J. M. Sullivan, B. R. Blazar, V. K. Kuchroo, and A. C. Anderson. 2010. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. [Published erratum appears in 2011 J. Exp. Med. 208: 1331.] J. Exp. Med. 207: 2187-2194.
19. Cheever, M. A. 2008. Twelve immunotherapy drugs that could cure cancers. Immunol. Rev. 222: 357-368.
20. Wu, J. 2013. IL-15 agonists: The cancer cure cytokine. J. Mol. Genet. Med. 7: 85.
21. Perdreau, H., E. Mortier, G. Bouchaud, V. Solé, Y. Boublik,A. Plet, andY. Jacques. 2010. Different dynamics of IL-15R activation following IL-15 cis-or transpresentation. Eur. Cytokine Netw. 21: 297-307.
22. Johnston, R. J., L. Comps-Agrar, J. Hackney, X. Yu, M. Huseni, Y. Yang, S. Park, V. Javinal, H. Chiu, B. Irving, et al. 2014. The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer Cell 26: 923-937.
23. Duraiswamy, J., K. M. Kaluza, G. J. Freeman, and G. Coukos. 2013. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res. 73: 3591-3603.
24. Kim, K., A. D. Skora, Z. Li, Q. Liu, A. J. Tam, R. L. Blosser, L. A. Diaz, Jr., N. Papadopoulos, K. W. Kinzler, B. Vogelstein, and S. Zhou. 2014. Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells. Proc. Natl. Acad. Sci. USA 111: 11774-11779.
25. Snyder, A., J. D. Wolchok, and T. A. Chan. 2015. Genetic basis for clinical response to CTLA-4 blockade. N. Engl. J. Med. 372: 783.
26. Van Allen, E. M., D. Miao, B. Schilling, S. A. Shukla, C. Blank, L. Zimmer, A. Sucker, U. Hillen, M. H. Foppen, S. M. Goldinger, et al. 2015. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350: 207-211.
27. Rizvi, N. A., M. D. Hellmann, A. Snyder, P. Kvistborg, V. Makarov, J. J. Havel, W. Lee, J. Yuan, P. Wong, T. S. Ho, et al. 2015. Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348: 124-128.
28. Le, D. T., J. N. Uram, H. Wang, B. R. Bartlett, H. Kemberling, A. D. Eyring, A. D. Skora, B. S. Luber, N. S. Azad, D. Laheru, et al. 2015. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 372: 2509-2520.
29. Yu, P., J. C. Steel, M. Zhang, J. C. Morris, R. Waitz, M. Fasso, J. P. Allison, and T. A. Waldmann. 2012. Simultaneous inhibition of two regulatory T-cell subsets enhanced interleukin-15 efficacy in a prostate tumor model. Proc. Natl. Acad. Sci. USA 109: 6187-6192.
30. Kinter, A. L., E. J. Godbout, J. P. McNally, I. Sereti, G. A. Roby, M. A. O'Shea, and A. S. Fauci. 2008. The common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J. Immunol. 181: 6738-6746.
31. Hsieh, C. S., S. E. Macatonia, A. O'Garra, and K. M. Murphy. 1995. T cell genetic background determines default T helper phenotype development in vitro. J. Exp. Med. 181: 713-721.
32. Corry, D. B., S. L. Reiner, P. S. Linsley, and R. M. Locksley. 1994. Differential effects of blockade of CD28-B7 on the development of Th1 or Th2 effector cells in experimental leishmaniasis. J. Immunol. 153: 4142-4148.
33. Johnston, C. E., J. E. Bradley, J. M. Behnke, K. R. Matthews, and K. J. Else. 2005. Isolates of Trichuris muris elicit different adaptive immune responses in their murine host. Parasite Immunol. 27: 69-78.
34. Aspord, C., M. T. Leccia, J. Charles, and J. Plumas. 2013. Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL. Cancer Immunol. Res. 1: 402-415.
35. Tosolini, M., A. Kirilovsky, B. Mlecnik, T. Fredriksen, S. Mauger, G. Bindea, A. Berger, P. Bruneval, W. H. Fridman, F. Pagès, and J. Galon. 2011. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res. 71: 1263-1271.
36. Nevala, W. K., C. M. Vachon, A. A. Leontovich, C. G. Scott, M. A. Thompson, S. N. Markovic, and Melanoma Study Group of the Mayo Clinic Cancer Center. 2009. Evidence of systemic Th2-driven chronic inflammation in patients with metastatic melanoma. Clin. Cancer Res. 15: 1931-1939.
37. Kusuda, T., K. Shigemasa, K. Arihiro, T. Fujii, N. Nagai, and K. Ohama. 2005. Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer. Oncol. Rep. 13: 1153-1158.
38. Robert, C., G. V. Long, B. Brady, C. Dutriaux, M. Maio, L. Mortier, J. C. Hassel, P. Rutkowski, C. McNeil, E. Kalinka-Warzocha, et al. 2015. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372: 320-330.
39. Robert, C., J. Schachter, G. V. Long, A. Arance, J. J. Grob, L. Mortier, A. Daud, M. S. Carlino, C. McNeil, M. Lotem, et al; KEYNOTE-006 Investigators. 2015. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N. Engl. J. Med. 372: 2521-2532.
40. Zhang, M., Z. Yao, S. Dubois, W. Ju, J. R. Muller, and T. A. Waldmann. 2009. Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer. Proc. Natl. Acad. Sci. USA 106: 7513-7518.