CXCR2-dependent accumulation of tumor-associated neutrophils regulates T-cell immunity in pancreatic ductal adenocarcinoma

Cancer Immunology Research

Volumn 4, Issue 11, 2016, Pages 968-982

  Chao, Timothy ^a   Furth, Emma E ^a,b   Vonderheide, Robert H ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; CD11B ANTIGEN; CD19 ANTIGEN; CD3 ANTIGEN; CD31 ANTIGEN; CD4 ANTIGEN; CD45 ANTIGEN; CD8ALPHA ANTIGEN; CHEMOKINE; CHEMOKINE RECEPTOR CXCR2; COLONY STIMULATING FACTOR; COLONY STIMULATING FACTOR 2; CXCL1 CHEMOKINE; CXCL2 CHEMOKINE; CXCL3 CHEMOKINE; CXCL7 CHEMOKINE; EPITHELIAL DERIVED NEUTROPHIL ACTIVATING FACTOR 78; GAMMA INTERFERON; GLYCOPROTEIN P 15095; HERMES ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 8; K RAS PROTEIN; L SELECTIN; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 1; TRANSCRIPTION FACTOR YAP1; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; WEDELOLACTONE; BIOLOGICAL MARKER; RAS PROTEIN; TRANSCRIPTOME;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN EXPRESSION; ARTICLE; CANCER INHIBITION; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DENSITY; CELL INFILTRATION; CELLULAR IMMUNITY; CONTROLLED STUDY; EFFECTOR CELL; GENE EXPRESSION; GENETIC ASSOCIATION; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; IMMUNOREGULATION; IN VITRO STUDY; INTRACELLULAR SIGNALING; LYMPHOCYTIC INFILTRATION; MOUSE; NEUTROPHIL; NONHUMAN; PANCREAS ADENOCARCINOMA; PANCREATIC CANCER CELL LINE; STROMA CELL; T CELL DEPLETION; T LYMPHOCYTE ACTIVATION; TUMOR ABLATION; TUMOR ASSOCIATED NEUTROPHIL; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; ANIMAL; ANTAGONISTS AND INHIBITORS; CLUSTER ANALYSIS; DISEASE MODEL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE INACTIVATION; GENETICS; IMMUNOLOGY; IMMUNOMODULATION; KNOCKOUT MOUSE; LYMPHOCYTE ACTIVATION; METABOLISM; NEUTROPHIL CHEMOTAXIS; PANCREAS CARCINOMA; PANCREAS TUMOR; PATHOLOGY; T LYMPHOCYTE; TUMOR CELL LINE;

ANIMALS; BIOMARKERS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; CHEMOKINE CXCL5; CLUSTER ANALYSIS; DISEASE MODELS, ANIMAL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE KNOCKOUT TECHNIQUES; HUMANS; IMMUNOMODULATION; LYMPHOCYTE ACTIVATION; MICE, KNOCKOUT; NEUTROPHIL INFILTRATION; NEUTROPHILS; NF-KAPPA B; PANCREATIC NEOPLASMS; RAS PROTEINS; RECEPTORS, INTERLEUKIN-8B; T-LYMPHOCYTES; TRANSCRIPTOME; TUMOR NECROSIS FACTOR-ALPHA;

EID: 85016124963     PISSN: 23266066     EISSN: 23266074     Source Type: Journal    
DOI: 10.1158/2326-6066.CIR-16-0188     Document Type: Article

References (62)

1. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-25.
2. Hoff Von DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-703.
3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7-30.
4. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014;74:2913-21.
5. Hanahan D, Weinberg R. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.
6. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005;7:469-83.
7. Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res 2007;67:9518-27.
8. Winograd R, Byrne KT, Evans RA, Odorizzi PM, Meyer ARL, Bajor DL, et al. Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma. Cancer Immun Res 2015;3:399-411.
9. Pylayeva-Gupta Y, Lee KE, Hajdu CH, Miller G, Bar-Sagi D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell 2012;21:836-47.
10. Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011;331: 1612-6.
11. Byrne KT, Vonderheide R. CD40 stimulation obviates innate sensors and drives T cell immunity in cancer. Cell Rep 2016;15:2719-32.
12. Beatty GL, Winograd R, Evans RA, Long K, Luque S, Lee JW, et al. Exclusion of T cells from pancreatic carcinomas in mice is regulated by Ly6C low F4/80+ extratumoral macrophages. Gastroenterology 2015; 149:201-10.
13. Bayne L, Beatty G, Jhala N, Clark C, Rhim A, Stanger B, et al. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic vancer. Cancer Cell 2012; 21:822-35.
14. Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer 2016;16:431-46.
15. Bronte V, Brandau S, Chen S-H, Colombo MP, Frey AB, Greten TF, et al. Recommendations formyeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 2016;7:12150.
16. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 2012;12:253-68.
17. Fridlender Z, Albelda S. Tumor-associated neutrophils: friend or foe? Carcinogenesis 2012;33:949-55.
18. Shen M, Hu P, Donskov F, Wang G, Liu Q, Du J. Tumor-associated neutrophils as a new prognostic factor in cancer: a systematic review and meta-analysis. PLoS ONE 2014;9:e98259.
19. Steele CW, Karim SA, Leach JDG, Bailey P, Upstill-Goddard R, Rishi L, et al. CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma. Cancer Cell 2016;29: 832-45.
20. Spiegel A, Brooks MW, Houshyar S, Reinhardt F, Ardolino M, Fessler E, et al. Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells. Cancer Discov 2016;6:630-49.
21. Shojaei F, Wu X, Zhong C, Yu L, Liang X-H, Yao J, et al. Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature 2007;450: 825-31.
22. Wculek SK, Malanchi I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature 2015;528:413-7.
23. Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, et al. Arginase I production in the tumor microenvironment by maturemyeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 2004;64:5839-49.
24. Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-b:"N1" versus 'N2' TAN. Cancer Cell 2009;16:183-94.
25. Singhal S, Bhojnagarwala PS, O'Brien S, Moon EK, Garfall AL, Rao AS, et al. Origin and role of a subset of tumor-associated neutrophils with antigenpresenting cell features in early-stage human lung cancer. Cancer Cell 2016;30:120-35.
26. Reid MD, Basturk O, Thirabanjasak D, Hruban RH, Klimstra DS, Bagci P, et al. Tumor-infiltrating neutrophils in pancreatic neoplasia. Mod Pathol 2011;24:1612-9.
27. Wang W-Q, Liu L, Xu H-X, Wu C-T, Xiang J-F, Xu J, et al. Intratumoral infiltrating immune cells and gene mutations in pancreatic ductal adenocarcinoma. Br J Surg 2016.
28. Li A, King J, Moro A, Sugi MD, Dawson DW, Kaplan J, et al. Overexpression of CXCL5 is associated with poor survival in patients with pancreatic cancer. Am J Pathol 2011;178:1340-9.
29. Stromnes IM, Brockenbrough JS, Izeradjene K, Carlson MA, Cuevas C, Simmons RM, et al. Targeted depletion of an MDSC subset unmasks pancreatic ductal adenocarcinoma to adaptive immunity. Gut 2014;63: 1769-81.
30. Eash KJ, Greenbaum AM, Gopalan PK, Link DC. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest 2010;120:2423-31.
31. Mei J, Liu Y, Dai N, Hoffmann C, Hudock KM, Zhang P, et al. Cxcr2 and Cxcl5 regulate the IL-17/G-CSF axis and neutrophil homeostasis in mice. J Clin Invest 2012;122:974-86.
32. Highfill SL, Cui Y, Giles AJ, Smith JP, Zhang H, Morse E, et al. Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci Translat Med 2014;6:237ra67.
33. Katoh H, Wang D, Daikoku T, Sun H, Dey S, DuBois R. CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis. Cancer Cell 2013;24:631-44.
34. Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Walder M, Obenauf AC, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013;39:782-95.
35. Bailey P, Chang DK, Nones K, Johns AL, Patch A-M, Gingras M-C, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 2016;531:47-52.
36. Collisson EA, Sadan A, am Olson P, Gibb WJ, Truitt M, et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med 2011;17:500-3.
37. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005;102:15545-50.
38. Rhim A, Mirek E, Aiello N, Maitra A, Bailey J, McAllister F, et al. EMT and dissemination precede pancreatic tumor formation. Cell 2012;148: 349-61.
39. Evans RA, Diamond M, Rech AJ, Chao T, Richardson M, Lin J, et al. Lack of immunoediting in murine pancreatic cancer reversedwith neo-antigen. JCI Insight 2016;1:e88328.
40. Stuart JM, Network CGAR. The cancer genome atlas pan-cancer analysis project. Nat Genet 2013;45:1113-20.
41. Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SGH, Hoadley KA, et al. Virtual microdissection identifies distinct tumor-and stromaspecific subtypes of pancreatic ductal adenocarcinoma. Nat Genet 2015;47:1168-78.
42. Lo A, Wang L-CS, Scholler J, Monslow J, Avery D, Newick K, et al. Tumorpromoting desmoplasia is disrupted by depleting FAP-expressing stromal cells. Cancer Res 2015;75:2800-10.
43. Zhang W, Nandakumar N, Shi Y, Manzano M, Smith A, Graham G, Gupta S, et al. Downstream of mutant KRAS, the transcription regulator YAP is essential for neoplastic progression to pancreatic ductal adenocarcinoma. Sci Signal 2014;7:ra42.
44. Wang G, Lu X, Dey P, Deng P, Wu CC, Jiang S, et al. Targeting YAPdependent MDSC infiltration impairs tumor progression. Cancer Discov 2016;6:80-95.
45. Ijichi H, Chytil A, Gorska AE, Aakre ME, Bierie B, Tada M, et al. Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma. J Clin Invest 2011; 121:4106-17.
46. Purohit A, Varney M, Rachagani S, Ouellette MM, Batra SK, Singh RK. CXCR2 signaling regulates KRAS (G12D)-induced autocrine growth of pancreatic cancer. Oncotarget 2016;7:7280-96.
47. Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med 2015;21:938-45.
48. Coffelt SB, Kersten K, Doornebal CW, Weiden J. IL-17-producing gd T cells and neutrophils conspire to promote breast cancer metastasis. Nature 2015;522:345-8.
49. Daley D, Zambirinis CP, Seifert L, Akkad N, Mohan N, Werba G, et al. gd T cells support pancreatic oncogenesis by restraining ab T cell activation. Cell 2016;166:1485-99.
50. Fridlender ZG, Sun J, Mishalian I, Singhal S, Cheng G, Kapoor V, et al. Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils. PLoS ONE 2012;7:e31524.
51. Seifert L, Werba G, Tiwari S, Ly NNG, Alothman S, Alqunaibit D, et al. The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincleinduced immune suppression. Nature 2016;532:245-9.
52. Hammond ME, Lapointe GR, Feucht PH, Hilt S, Gallegos CA, Gordon CA, et al. IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors. J Immunol 1995;155:1428-33.
53. Zlotnik A, Yoshie O. The chemokine superfamily revisited. Immunity 2012;36:705-16.
54. Alfaro C, Teijeira A, Oñate C, Pérez G, Sanmamed MF, Andueza MP, et al. Tumor-produced interleukin-8 attracts human myeloid-derived suppressor cells and elicits extrusion of neutrophil extracellulartraps (NETs). Clin Cancer Res 2016;22:3924-36.
55. Lesina M, Wörmann SM, Morton J, Diakopoulos KN, Korneeva O, Wimmer M, et al. RelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis. J Clin Invest 2016;126:2919-32.
56. Wang WX, Abbruzzese JL, Evans DB, Larry L, Cleary KR, Chiao PJ. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res 1999;5:119-27.
57. Ling J, Kang Y, Zhao R, Xia Q, Lee DF, Chang Z, et al. Kras G12D-induced IKK2/b/NF-kB activation by IL-1a and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma. Cancer Cell 2012;21:105-20.
58. Wee S, Jagani Z, Xiang KX, Loo A, Dorsch M, Yao Y-M, et al. PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant cancers. Cancer Res 2009;69:4286-93.
59. Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ, Cusworth BM, et al. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol 2016;17:651-62.
60. Jiang H, Hegde S, Knolhoff BL, Zhu Y, Herndon JM, Meyer MA, et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med 2016;22:851-60.
61. Feig C, Jones JO, Kraman M, Wells RJB, Deonarine A, Chan DS, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA 2013;110:20212-7.
62. Sparmann A, Bar-Sagi D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 2004;6:447-58.