Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer

Nature Communications

Volumn 8, Issue , 2017, Pages

  Carstens, Julienne L ^a   De Sampaio, Pedro Correa ^a   Yang, Dalu ^a,b   Barua, Souptik ^a,b   Wang, Huamin ^a   Rao, Arvind ^a,b   Allison, James P ^a   Le Bleu, Valerie S ^a   Kalluri, Raghu ^a,b,c  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b Rice University   (United States)

^c BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; CD3 ANTIGEN; CD4 ANTIGEN; CD8 ANTIGEN; COLLAGEN TYPE 1; CYTOKERATIN 8; TRANSCRIPTION FACTOR FOXP3; ACTA2 PROTEIN, HUMAN; ACTIN;

CANCER; CELLS AND CELL COMPONENTS; COLLAGEN; GENETIC MARKER; IMMUNE RESPONSE; IMMUNITY; OPTIMIZATION; SPATIAL ANALYSIS; SPATIAL DISTRIBUTION; SURVIVAL;

ARTICLE; CANCER SURVIVAL; CD4+ T LYMPHOCYTE; CYTOTOXIC T LYMPHOCYTE; FIBROBLAST; HUMAN; HUMAN TISSUE; LYMPHOCYTIC INFILTRATION; MAJOR CLINICAL STUDY; OVERALL SURVIVAL; PANCREAS ADENOCARCINOMA; PHENOTYPE; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TISSUE MICROARRAY; ADULT; AGED; ANIMAL; FEMALE; IMMUNOHISTOCHEMISTRY; MALE; METABOLISM; MIDDLE AGED; MORTALITY; MOUSE; PANCREAS CARCINOMA; PANCREAS TUMOR; PATHOLOGY; PROCEDURES; PROGNOSIS; SPATIAL ANALYSIS; SPECTROSCOPY; SURVIVAL RATE; TUMOR ASSOCIATED LEUKOCYTE; VERY ELDERLY;

ACTINS; ADULT; AGED; AGED, 80 AND OVER; ANIMALS; CARCINOMA, PANCREATIC DUCTAL; COLLAGEN TYPE I; FEMALE; FIBROBLASTS; HUMANS; IMMUNOHISTOCHEMISTRY; LYMPHOCYTES, TUMOR-INFILTRATING; MALE; MICE; MIDDLE AGED; PANCREATIC NEOPLASMS; PROGNOSIS; SPATIAL ANALYSIS; SPECTRUM ANALYSIS; SURVIVAL RATE; T-LYMPHOCYTES; T-LYMPHOCYTES, CYTOTOXIC; TISSUE ARRAY ANALYSIS;

EID: 85029636194     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms15095     Document Type: Article

References (37)

1. Vonderheide, R. H. & Bayne, L. J. Inflammatory networks and immune surveillance of pancreatic carcinoma. Curr. Opin. Immunol. 25, 200-205 (2013).
2. Schmitz-Winnenthal, F. H. et al. High frequencies of functional tumour-reactive T cells in bone marrow and blood of pancreatic cancer patients. Cancer Res. 65, 10079-10087 (2005).
3. Shibuya, K. C. et al. Pancreatic ductal adenocarcinoma contains an effector and regulatory immune cell infiltrate that is altered by multimodal neoadjuvant treatment. PLoS ONE 9, e96565 (2014).
4. Fukunaga, A. et al. CD8 + tumour-infiltrating lymphocytes together with CD4 + tumour-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas 28, e26-31 (2004).
5. Ene-Obong, A. et al. Activated pancreatic stellate cells sequester CD8 + T cells to reduce their infiltration of the juxtatumoral compartment of pancreatic ductal adenocarcinoma. Gastroenterology 145, 1121-1132 (2013).
6. Ino, Y. et al. Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br. J. Cancer 108, 914-923 (2013).
7. Clark, C. E. et al. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res. 67, 9518-9527 (2007).
8. Alrifai, D., Sarker, D. & Maher, J. Prospects for adoptive immunotherapy of pancreatic cancer using chimeric antigen receptor-engineered T-cells. Immunopharmacol. Immunotoxicol. 38, 50-60 (2016).
9. Feig, C. et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc. Natl Acad. Sci. USA 110, 20212-20217 (2013).
10. Jiang, H. et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat. Med. 22, 851-860 (2016).
11. Hiraoka, N., Onozato, K., Kosuge, T. & Hirohashi, S. Prevalence of FOXP3 + regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin. Cancer Res. 12, 5423-5434 (2006).
12. Tassi, E. et al. Carcinoembryonic antigen-specific but not antiviral CD4 + T cell immunity is impaired in pancreatic carcinoma patients. J. Immunol. 181, 6595-6603 (2008).
13. De Monte, L. et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J. Exp. Med. 208, 469-478 (2011).
14. Ozdemir, B. C. et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell 25, 719-734 (2014).
15. Soares, K. C. et al. TGF-beta blockade depletes T regulatory cells from metastatic pancreatic tumours in a vaccine dependent manner. Oncotarget 6, 43005-43015 (2015).
16. Soares, K. C. et al. PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumours. J. Immunother. 38, 1-11 (2015).
17. + extratumoral macrophages. Gastroenterology 149, 201-210 (2015).
18. Schueneman, A. J. et al. Low total lymphocyte count is associated with poor survival in patients with resected pancreatic adenocarcinoma receiving a GM-CSF secreting pancreatic tumour vaccine. Ann. Surg. Oncol. 20, S725-S730 (2013).
19. Winograd, R. et al. Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma. Cancer Immunol. Res. 3, 399-411 (2015).
20. Besag, J. Comments on Ripley's paper. J. R. Stat. Soc. B 39, 193-195 (1977).
21. Ripley, B. The second-order analysis of stationary point processes. J. Appl. Prob. 13, 255-266 (1976).
22. Heindl, A., Nawaz, S. & Yuan, Y. Mapping spatial heterogeneity in the tumour microenvironment: a new era for digital pathology. Lab. Invest. 95, 377-384 (2015).
23. Yuan, Y. et al. Quantitative image analysis of cellular heterogeneity in breast tumours complements genomic profiling. Sci. Transl. Med. 4, 157ra143 (2012).
24. Janeway, C., Travers, P. & Walport, M. Immunobiology: the Immune System in Health and Disease 5th edn (Garland Science, 2001).
25. Wartenberg, M. et al. Accumulation of FOXP3 + T-cells in the tumour microenvironment is associated with an epithelial-mesenchymal-transition-type tumour budding phenotype and is an independent prognostic factor in surgically resected pancreatic ductal adenocarcinoma. Oncotarget 6, 4190-4201 (2015).
26. Hinz, S. et al. Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res. 67, 8344-8350 (2007).
27. Lutz, E. R. et al. Immunotherapy converts nonimmunogenic pancreatic tumours into immunogenic foci of immune regulation. Cancer Immunol. Res. 2, 616-631 (2014).
28. Feng, Z. et al. Multispectral imaging of formalin-fixed tissue predicts ability to generate tumour-infiltrating lymphocytes from melanoma. J. Immunother. Cancer 3, 1-11 (2015).
29. Royal, R. E. et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J. Immunother. 33, 828-833 (2010).
30. Redman, J. M., Gibney, G. T. & Atkins, M. B. Advances in immunotherapy for melanoma. BMC Med. 14, 20 (2016).
31. Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568-571 (2014).
32. Haanen, J. B. Immunotherapy of melanoma. EJC Suppl. 11, 97-105 (2013).
33. Galon, J. et al. Cancer classification using the Immunoscore: a worldwide task force. J. Transl. Med. 10, 205 (2012).
34. Wang, H., Wang, H., Zhang, W. & Fuller, G. N. Tissue microarrays: applications in neuropathology research, diagnosis, and education. Brain Pathol. 12, 95-107 (2002).
35. Wang, O. H. et al. Prognostic and functional significance of MAP4K5 in pancreatic cancer. PLoS ONE 11, e0152300 (2016).
36. Harkness, R. & Isham, V. A bivariate spatial point pattern of ants' nests. Appl. Stat. 32, 293-303 (1983).
37. Baddeley, A., Rubak, E. & Turner, R. Spatial Point Patterns: Methodology and Applications with R (CRC Press, 2015).