Tumor-infiltrating and peripheral blood T-cell immunophenotypes predict early relapse in localized clear cell renal cell carcinoma

Clinical Cancer Research

Volumn 23, Issue 15, 2017, Pages 4416-4428

  Giraldo, Nicolas A ^a,b,c,g   Becht, Etienne ^a,b,c   Vano, Yann ^a,b,c,d   Petitprez, Florent ^a,b,c,e   Lacroix, Laetitia ^a,b,c   Validire, Pierre ^f   Sanchez Salas, Rafael ^f   Ingels, Alexandre ^f   Oudard, Stephane ^d   Moatti, Audrey ^a,b,c   Buttard, Benedicte ^a,b,c   Bourass, Sarah ^a,b,c   Germain, Claire ^a,b,c   Cathelineau, Xavier ^b,f   Fridman, Wolf H ^a,b,c   Sautes Fridman, Catherine ^a,b,c  

^a INSERM   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

^c SORBONNE UNIVERSITÉ   (France)

^d HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

^e Cartes d'Identité des Tumeurs Program Ligue Nationale Contre le Cancer   (France)

^f INSTITUT MUTUALISTE MONTSOURIS   (France)

^g DEPARTMENT OF PATHOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD8 ANTIGEN; HEPATITIS A VIRUS CELLULAR RECEPTOR 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 7 RECEPTOR; PROGRAMMED DEATH 1 LIGAND 1; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; TUMOR PROTEIN;

ARTICLE; CANCER GROWTH; CANCER LOCALIZATION; CANCER RECURRENCE; CELL SELECTION; CLINICAL ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IMMUNOPHENOTYPING; IMMUNOREGULATION; KIDNEY CARCINOMA; NEPHRECTOMY; PERIPHERAL LYMPHOCYTE; PRIORITY JOURNAL; PROGNOSTIC ASSESSMENT; QUANTITATIVE ANALYSIS; T LYMPHOCYTE; TUMOR ASSOCIATED LEUKOCYTE; AGED; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; DENDRITIC CELL; FEMALE; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; MALE; MIDDLE AGED; PATHOLOGY; PROGNOSIS; RENAL CELL CARCINOMA; TUMOR RECURRENCE;

AGED; CARCINOMA, RENAL CELL; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; DENDRITIC CELLS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMMUNOPHENOTYPING; LYMPHOCYTES, TUMOR-INFILTRATING; MALE; MIDDLE AGED; NEOPLASM PROTEINS; NEOPLASM RECURRENCE, LOCAL; PROGNOSIS; T-LYMPHOCYTES;

EID: 85018512066     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-16-2848     Document Type: Article

References (50)

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646–74.
2. Giraldo NA, Becht E, Vano Y, Sautes-Fridman C, Fridman WH. The immune response in cancer: from immunology to pathology to immunotherapy. Virchows Arch Int J Pathol 2015;467:127–35.
3. Becht E, Giraldo NA, Germain C, de Reynies A, Laurent-Puig P, Zucman-Rossi J, et al. Immune contexture, immunoscore, and malignant cell molecular subgroups for prognostic and theranostic classifications of cancers. Adv Immunol 2016;130:95–190.
4. Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 2012;12: 298–306.
5. Giraldo NA, Becht E, Pages F, Skliris G, Verkarre V, Vano Y, et al. Orchestration and prognostic significance of immune checkpoints in the microenvironment of primary and metastatic renal cell cancer. Clin Cancer Res 2015;21:3031–40.
6. Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, et al. Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 2001;61:5132–6.
7. Scott DW, Chan FC, Hong F, Rogic S, Tan KL, Meissner B, et al. Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical Hodgkin lymphoma. J Clin Oncol 2013;31:692–700.
8. Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, et al. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2016 Jan 22. [Epub ahead of print].
9. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 2014;20: 5064–74.
10. Teng MWL, Ngiow SF, Ribas A, Smyth MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res 2015;75:2139–45.
11. Goc J, Germain C, Vo-Bourgais TKD, Lupo A, Klein C, Knockaert S, et al. Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer Res 2014;74:705–15.
12. Tokito T, Azuma K, Kawahara A, Ishii H, Yamada K, Matsuo N, et al. Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy. Eur J Cancer 2016;55:7–14.
13. Becht E, de Reynies A, Giraldo NA, Pilati C, Buttard B, Lacroix L, et al. Immune and stromal classification of colorectal cancer is associated with molecular subtypes and relevant for precision immunotherapy. Clin Cancer Res 2016;22:4057–66.
14. Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 2016;165:35–44.
15. Lipson EJ, Forde PM, Hammers H-J, Emens LA, Taube JM, Topalian SL. Antagonists of PD-1 and PD-L1 in cancer treatment. Semin Oncol 2015; 42:587–600.
16. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015; 348:124–8.
17. Duraiswamy J, Freeman GJ, Coukos G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors–response. Cancer Res 2014;74:633–4; discussion 635.
18. Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity 2016;44:989–1004.
19. Roederer M, Nozzi JL, Nason MC. SPICE: exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A 2011;79A: 167–74.
20. Stewart JJ, Lee CY, Ibrahim S, Watts P, Shlomchik M, Weigert M, et al. A Shannon entropy analysis of immunoglobulin and T cell receptor. Mol Immunol 1997;34:1067–82.
21. Tibshirani R, Walther G, Hastie T. Estimating the number of clusters in a data set via the gap statistic. J R Stat Soc Ser B Stat Methodol 2001;63:411–23.
22. Thompson RH, Dong H, Lohse CM, Leibovich BC, Blute ML, Cheville JC, et al. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res 2007;13:1757–61.
23. Faget J, Bendriss-Vermare N, Gobert M, Durand I, Olive D, Biota C, et al. ICOS-ligand expression on plasmacytoid dendritic cells supports breast cancer progression by promoting the accumulation of immunosuppressive CD4+ T cells. Cancer Res 2012;72:6130–41.
24. Ye Q, Song D-G, Poussin M, Yamamoto T, Best A, Li C, et al. CD137 accurately identifies and enriches for naturally occurring tumor-reactive T cells in tumor. Clin Cancer Res 2014;20:44–55.
25. + tumor-reactive repertoire infiltrating human tumors. J Clin Invest 2014;124:2246–59.
26. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 2012;4:127ra37.
27. Mlecnik B, Bindea G, Angell HK, Maby P, Angelova M, Tougeron D, et al. Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability. Immunity 2016;44:698–711.
28. Sittig SP, Køllgaard T, Grønbæk K, Idorn M, Hennenlotter J, Stenzl A, et al. Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes. Oncoimmunology 2013;2:e26014.
29. Dannenmann SR, Thielicke J, Stöckli M, Matter C, von Boehmer L, Cecconi V, et al. Tumor-associated macrophages subvert T-cell function and correlate with reduced survival in clear cell renal cell carcinoma. Oncoimmunology 2013;2:e23562.
30. Beuselinck B, Job S, Becht E, Karadimou A, Verkarre V, Couchy G, et al. Molecular subtypes of clear cell renal cell carcinoma are associated with sunitinib response in the metastatic setting. Clin Cancer Res 2015;21: 1329–39.
31. Pierorazio PM, Johnson MH, Ball MW, Gorin MA, Trock BJ, Chang P, et al. Five-year analysis of a multi-institutional prospective clinical trial of delayed intervention and surveillance for small renal masses: the DISSRM registry. Eur Urol 2015;68:408–15.
32. Skinnider BF, Folpe AL, Hennigar RA, Lim SD, Cohen C, Tamboli P, et al. Distribution of cytokeratins and vimentin in adult renal neoplasms and normal renal tissue: potential utility of a cytokeratin antibody panel in the differential diagnosis of renal tumors. Am J Surg Pathol 2005;29:747–54.
33. Legat A, Speiser DE, Pircher H, Zehn D, Fuertes Marraco SA. Inhibitory receptor expression depends more dominantly on differentiation and activation than "Exhaustion" of human CD8 T cells. Front Immunol 2013; 4:455.
34. Inozume T, Hanada K-I, Wang QJ, Ahmadzadeh M, Wunderlich JR, Rosenberg SA, et al. Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. J Immunother 2010;33: 956–64.
35. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015;15:486–99.
36. Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 2009;114:1537–44.
37. Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res 2013; 73:128–38.
38. Webb JR, Milne K, Nelson BH. PD-1 and CD103 are widely coexpressed on prognostically favorable intraepithelial CD8 T cells in human ovarian cancer. Cancer Immunol Res 2015;3:926–35.
39. Becht E, Giraldo NA, Dieu-Nosjean M-C, Sautes-Fridman C, Fridman WH. Cancer immune contexture and immunotherapy. Curr Opin Immunol 2016;39:7–13.
40. Griffiths RW, Elkord E, Gilham DE, Ramani V, Clarke N, Stern PL, et al. Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival. Cancer Immunol Immunother CII 2007;56:1743–53.
41. Li JF, Chu YW, Wang GM, Zhu TY, Rong RM, Hou J, et al. The prognostic value of peritumoral regulatory T cells and its correlation with intratumoral cyclooxygenase-2 expression in clear cell renal cell carcinoma. BJU Int 2009;103:399–405.
42. Kang MJ, Kim KM, Bae JS, Park HS, Lee H, Chung MJ, et al. Tumor-infiltrating PD1-positive lymphocytes and FoxP3-positive regulatory T cells predict distant metastatic relapse and survival of clear cell renal cell carcinoma. Transl Oncol 2013;6:282–9.
43. Kim H-J, Barnitz RA, Kreslavsky T, Brown FD, Moffett H, Lemieux ME, et al. Stable inhibitory activity of regulatory T cells requires the transcription factor Helios. Science 2015;350:334–9.
44. Nakagawa H, Sido JM, Reyes EE, Kiers V, Cantor H, Kim H-J. Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity. Proc Natl Acad Sci U S A 2016;113:6248–53.
45. Desar IME, Jacobs JHFM, Hulsbergen-vandeKaa CA, Oyen WJG, Mulders PFA, van der Graaf WTA, et al. Sorafenib reduces the percentage of tumour infiltrating regulatory T cells in renal cell carcinoma patients. Int J Cancer 2011;129:507–12.
46. Gerlinger M, Quezada SA, Peggs KS, Furness AJ, Fisher R, Marafioti T, et al. Ultra-deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas: ultra-deep sequencing of T cell repertoires in renal cancer. J Pathol 2013; 231:424–32.
47. Gigante M, Blasi A, Loverre A, Mancini V, Battaglia M, Selvaggi FP, et al. Dysfunctional DC subsets in RCC patients: ex vivo correction to yield an effective anti-cancer vaccine. Mol Immunol 2009;46: 893–901.
48. Figel A-M, Brech D, Prinz PU, Lettenmeyer UK, Eckl J, Turqueti-Neves A, et al. Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations. Am J Pathol 2011; 179:436–51.
49. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012;12:265–77.
50. Kim C-S, Kim Y, Kwon T, Yoon JH, Kim KH, You D, et al. Regulatory T cells and TGF-β1 in clinically localized renal cell carcinoma: comparison with age-matched healthy controls. Urol Oncol 2015;33:113.e19–25.