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Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy

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Abstract

The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described “vaccinal effect” exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets (“conventional” CD4+ and CD8+, FOXP3+CD25bright Treg, and “innate-like” CD56+) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4+ T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4+ T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4+ and CD8+ T cell subsets associated with higher frequencies of IFNγ+ and GrzB+ cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.

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Abbreviations

ABC:

Activated B cell-like

ALC:

Absolute lymphocyte count

APC:

Allophycocyanin

DLBCL:

Diffuse large B-cell lymphoma

GCB:

Germinal center B cell-like

GrzB:

Granzyme B

R-CHOP:

Rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone chemoimmunotherapy

Treg:

Regulatory T cells

References

  1. Martelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA (2013) Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol 87:146–171. doi:10.1016/j.critrevonc.2012.12.009

    Article  PubMed  Google Scholar 

  2. Sehn LH, Gascoyne RD (2015) Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood 125:22–32. doi:10.1182/blood-2014-05-577189

    Article  CAS  PubMed  Google Scholar 

  3. Rosenwald A, Wright G, Chan WC et al (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346:1937–1947. doi:10.1056/NEJMoa012914

    Article  PubMed  Google Scholar 

  4. Vaidya R, Witzig TE (2014) Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era. Ann Oncol 25:2124–2133. doi:10.1093/annonc/mdu109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Selenko N, Maidic O, Draxier S, Berer A, Jäger U, Knapp W, Stöckl J (2001) CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells. Leukemia 15:1619–1626

    Article  CAS  PubMed  Google Scholar 

  6. Hilchey SP, Hyrien O, Mosmann TR, Livingstone AM, Friedberg JW, Young F, Fisher RI, Kelleher RJ Jr, Bankert RB, Bernstein SH (2009) Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a “vaccinal effect” of rituximab. Blood 113:3809–3812. doi:10.1182/blood-2008-10-185280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Abès R, Gélizé E, Fridman WH, Teillaud JL (2010) Long-lasting antitumor protection by anti-CD20 antibody through cellular immune response. Blood 116:926–934. doi:10.1182/blood-2009-10-248609

    Article  PubMed  Google Scholar 

  8. Michaud HA, Eliaou JF, Lafont V, Bonnefoy N, Gros L (2014) Tumor antigen-targeting monoclonal antibody-based immunotherapy: orchestrating combined strategies for the development of long-term antitumor immunity. Oncoimmunology 3:e955684. doi:10.4161/21624011.2014.955684

    Article  PubMed  PubMed Central  Google Scholar 

  9. Vanneman M, Dranoff G (2012) Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 12:237–251. doi:10.1038/nrc3237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G (2015) Immunological effects of conventional chemotherapy and targeted anticancer agents. Cancer Cell 28:690–714. doi:10.1016/j.ccell.2015

    Article  CAS  PubMed  Google Scholar 

  11. Manzur S, Cohen S, Haimovich J, Hollander N (2012) Enhanced therapeutic effect of B cell-depleting anti-CD20 antibodies upon combination with in situ dendritic cell vaccination in advanced lymphoma. Clin Exp Immunol 170(3):291–299. doi:10.1111/j.1365-2249.2012.04658.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Houot R, Kohrt H (2014) CD137 stimulation enhances the vaccinal effect of anti-tumor antibodies. Oncoimmunology 3:e941740. doi:10.4161/21624011.2014.941740

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lipowska-Bhalla G, Fagnano E, Illidge TM, Cheadle EJ (2016) Improving therapeutic activity of anti-CD20 antibody therapy through immunomodulation in lymphoid malignancies. Leuk Lymphoma 57:1269–1280. doi:10.3109/10428194.2016.1157874

    Article  CAS  PubMed  Google Scholar 

  14. Nelson MH, Paulos CM (2015) Novel immunotherapies for hematologic malignancies. Immunol Rev 263:90–105. doi:10.1111/imr.12245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Taylor JG, Gribben JG (2015) Microenvironment abnormalities and lymphomagenesis: immunological aspects. Semin Cancer Biol 34:36–45. doi:10.1016/j.semcancer.2015.07.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yang ZZ, Liang AB, Ansell SM (2015) T-cell-mediated antitumor immunity in B-cell non-Hodgkin lymphoma: activation, suppression and exhaustion. Leuk Lymphoma 56:2498–2504. doi:10.3109/10428194.2015.1011640

    Article  PubMed  Google Scholar 

  17. Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6:836–848. doi:10.1038/nri1961

    Article  CAS  PubMed  Google Scholar 

  18. Haabeth OA, Lorvik KB, Hammarström C, Donaldson IM, Haraldsen G, Bogen B, Corthay A (2011) Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nat Commun 2:240. doi:10.1038/ncomms1239

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ding ZC, Huang L, Blazar BR, Yagita H, Mellor AL, Munn DH, Zhou G (2012) Polyfunctional CD4+ T cells are essential for eradicating advanced B-cell lymphoma after chemotherapy. Blood 120:2229–2239. doi:10.1182/blood-2011-12-398321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lindqvist CA, Loskog AS (2012) T regulatory cells in B-cell malignancy—tumour support or kiss of death? Immunology 135:255–260. doi:10.1111/j.1365-2567.2011.03539.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Woo SR, Corrales L, Gajewski TF (2015) Innate immune recognition of cancer. Annu Rev Immunol 33:445–474. doi:10.1146/annurev-immunol-032414-112043

    Article  CAS  PubMed  Google Scholar 

  22. Tadmor T, Bari A, Sacchi S, Marcheselli L, Liardo EV, Avivi I, Benyamini N, Attias D, Pozzi S, Cox MC, Baldini L, Brugiatelli M, Federico M, Polliack A (2014) Monocyte count at diagnosis is a prognostic parameter in diffuse large B-cell lymphoma: results from a large multicenter study involving 1191 patients in the pre- and post-rituximab era. Haematologica 99:125–1230. doi:10.3324/haematol.2013.088161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Azzaoui I, Uhel F, Rossille D, Pangault C, Dulong J, Le Priol J, Lamy T, Houot R, Le Gouill S, Cartron G, Godmer P, Bouabdallah K, Milpied N, Damaj G, Tarte K, Fest T, Roussel M (2016) T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid derived suppressor cells expressing IL-10, PD-L1 and S100A12. Blood 128:1081–1092. doi:10.1182/blood-2015-08-662783

    Article  CAS  PubMed  Google Scholar 

  24. Charbonneau B, Maurer MJ, Ansell SM, Slager SL, Fredericksen ZS, Ziesmer SC, Macon WR, Habermann TM, Witzig TE, Link BK, Cerhan JR, Novak AJ (2012) Pretreatment circulating serum cytokines associated with follicular and diffuse large B-cell lymphoma: a clinic-based case-control study. Cytokine 60:882–889. doi:10.1016/j.cyto.2012.08.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pedersen LM, Klausen TW, Davidsen UH, Johnsen HE (2005) Early changes in serum IL-6 and VEGF levels predict clinical outcome following first-line therapy in aggressive non-Hodgkin’s lymphoma. Ann Hematol 84:510–516. doi:10.1007/s00277-005-1020-x

    Article  CAS  PubMed  Google Scholar 

  26. Galand C, Donnou S, Molina TJ, Fridman WH, Fisson S, Sautès-Fridman C (2012) Influence of tumor location on the composition of immune infiltrate and its impact on patient survival lessons from DCBCL and animal models. Front Immunol 3:98. doi:10.3389/fimmu.2012.00098

    Article  PubMed  PubMed Central  Google Scholar 

  27. Keane C, Vari F, Hertzberg M, Cao KA, Green MR, Han E, Seymour JF, Hicks RJ, Gill D, Crooks P, Gould C, Jones K, Griffiths LR, Talaulikar D, Jain S, Tobin J, Gandhi MK (2015) Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: a population-based study. Lancet Haematol 2:e445–e455. doi:10.1016/S2352-3026(15)00150-7

    Article  PubMed  Google Scholar 

  28. Xiao T, Zhang L, Chen L, Liu G, Feng Z, Gao L (2014) Tim-3 expression is increased on peripheral T cells from diffuse large B cell lymphoma. Tumour Biol 35:7951–7956. doi:10.1007/s13277-014-2080-0

    Article  CAS  PubMed  Google Scholar 

  29. Głowala-Kosińska M, Chwieduk A, Nieckula J, Saduś-Wojciechowska M, Grosicki S, Rusin A, Nowara E, Giebel S (2013) Association of circulating regulatory T cell number with the incidence and prognosis of diffuse large B-cell lymphoma. Eur J Haematol 91:122–128. doi:10.1111/ejh.12144

    Article  PubMed  Google Scholar 

  30. Cox MC, Nofroni I, Ruco L, Amodeo R, Ferrari A, La Verde G, Cardelli P, Montefusco E, Conte E, Monarca B, Aloe-Spiriti MA (2008) Low absolute lymphocyte count is a poor prognostic factor in diffuse-large-B-cell-lymphoma. Leuk Lymphoma 49:1745–1751. doi:10.1080/10428190802226425

    Article  PubMed  Google Scholar 

  31. Wilcox RA, Ristow K, Habermann TM, Inwards DJ, Micallef IN, Johnston PB, Colgan JP, Nowakowski GS, Ansell SM, Witzig TE, Markovic SN, Porrata L (2011) The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma. Leukemia 25:1502–1509. doi:10.1038/leu.2011.112

    Article  CAS  PubMed  Google Scholar 

  32. Porrata LF, Ristow K, Habermann TM, Ozsan N, Dogan A, Macon W, Colgan JP, Witzig TE, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Nowakowski GS, Thompson C, Markovic SN (2012) Absolute monocyte/lymphocyte count prognostic score is independent of immunohistochemically determined cell of origin in predicting survival in diffuse large B-cell lymphoma. Leuk Lymphoma 53:2159–2165. doi:10.3109/10428194.2012.690605

    Article  PubMed  Google Scholar 

  33. Lin B, Chen C, Qian Y, Feng J (2015) Prognostic role of peripheral blood lymphocyte/monocyte ratio at diagnosis in diffuse large B-cell lymphoma: a meta-analysis. Leuk Lymphoma 56:2563–2568. doi:10.3109/10428194.2015.1014367

    Article  PubMed  Google Scholar 

  34. Porrata LF, Ristow KM, Habermann TM, Witzig TE, Colgan JP, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Nowakowski G, Thompson CA, Markovic SN (2014) Peripheral blood absolute lymphocyte/monocyte ratio during rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone treatment cycles predicts clinical outcomes in diffuse large B-cell lymphoma. Leuk Lymphoma 55:2728–2738. doi:10.3109/10428194.2014.893313

    Article  CAS  PubMed  Google Scholar 

  35. Porrata LF, Rsitow K, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Habermann TM, Witzig TE, Colgan JP, Nowakowski GS, Thompson CA, Markovic SN (2010) Lymphopenia assessed during routine follow-up after immunochemotherapy (R-CHOP) is a risk factor for predicting relapse in patients with diffuse large B-cell lymphoma. Leukemia 24:1343–1349. doi:10.1038/leu.2010.108

    Article  CAS  PubMed  Google Scholar 

  36. Cox MC, Battella S, La Scaleia R, Pelliccia S, Di Napoli A, Porzia A, Cecere F, Alma E, Zingoni A, Mainiero F, Ruco L, Monarca B, Santoni A, Palmieri G (2015) Tumor-associated and immunochemotherapy-dependent long-term alterations of the peripheral blood NK cell compartment in DLBCL patients. Oncoimmunology 4:e990773. doi:10.4161/2162402X.2014.990773

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Müller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282. doi:10.1182/blood-2003-05-1545

    Article  CAS  PubMed  Google Scholar 

  38. Klimo P, Connors JM (1985) MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med 102:596–602

    Article  CAS  PubMed  Google Scholar 

  39. Cheson BD, Pfistner B, Juweid ME et al (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25:579–586. doi:10.1200/JCO.2006.09.2403

    Article  PubMed  Google Scholar 

  40. Maurer MJ, Ghesquières H, Jais JP, Witzig TE, Haioun C, Thompson CA, Delarue R, Micallef IN, Peyrade F, Macon WR, Jo Molina T, Ketterer N, Syrbu SI, Fitoussi O, Kurtin PJ, Allmer C, Nicolas-Virelizier E, Slager SL, Habermann TM, Link BK, Salles G, Tilly H, Cerhan JR (2014) Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol 32:1066–1073. doi:10.1200/JCO.2013.51.5866

    Article  PubMed  PubMed Central  Google Scholar 

  41. Piro LD, White CA, Grillo-López AJ, Janakiraman N, Saven A, Beck TM, Varns C, Shuey S, Czuczman M, Lynch JW, Kolitz JE, Jain V (1999) Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin’s lymphoma. Ann Oncol 10:655–661

    Article  CAS  PubMed  Google Scholar 

  42. Gergely L, Aleksza M, Váróczy L, Ponyi A, Sipka S, Illés A, Szegedi G (2004) Intracellular IL-4/IFN-gamma producing peripheral T lymphocyte subsets in B cell non-Hodgkin’s lymphoma patients. Eur J Haematol 72:336–341. doi:10.1111/j.1600-0609.2004.00234.x

    Article  CAS  PubMed  Google Scholar 

  43. Atanackovic D, Panse J, Schafhausen P, Faltz C, Bartels K, Boeters I, Hossfeld DK, Hegewisch-Becker S (2005) Peripheral T cells of patients with B cell non-Hodgkin’s lymphoma show a shift in their memory status. Leuk Res 29:1019–1027. doi:10.1016/j.leukres.2005.02.009

    Article  CAS  PubMed  Google Scholar 

  44. Ait-Tahar K, Liggins AP, Collins GP, Campbell A, Barnardo M, Cabes M, Lawrie CH, Moir D, Hatton C, Banham AH, Pulford K (2011) CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma. Haematologica 96:78–86. doi:10.3324/haematol.2010.028241

    Article  CAS  PubMed  Google Scholar 

  45. Lam LT, Wright G, Davis RE, Lenz G, Farinha P, Dang L, Chan JW, Rosenwald A, Gascoyne RD, Staudt LM (2008) Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-{kappa}B pathways in subtypes of diffuse large B-cell lymphoma. Blood 111:3701–3713. doi:10.1182/blood-2007-09-111948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gupta M, Han JJ, Stenson M, Maurer M, Wellik L, Hu G, Ziesmer S, Dogan A, Witzig TE (2012) Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation. Blood 119:2844–2853. doi:10.1182/blood-2011-10-388538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Keane C, Gill D, Vari F, Cross D, Griffiths L, Gandhi M (2013) CD4(+) tumor infiltrating lymphocytes are prognostic and independent of R-IPI in patients with DLBCL receiving R-CHOP chemo-immunotherapy. Am J Hematol 88:273–276. doi:10.1002/ajh.23398

    Article  CAS  PubMed  Google Scholar 

  48. Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G, Murty VV, Dominguez-Sola D, Pasqualucci L, Dalla-Favera R (2011) Combined genetic inactivation of β2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell 20:728–740. doi:10.1016/j.ccr.2011.11.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Andorsky DJ, Yamada RE, Said J, Pinkus GS, Betting DJ, Timmerman JM (2011) Programmed death ligand 1 is expressed by non-hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res 17:4232–4244. doi:10.1158/1078-0432.CCR-10-2660

    Article  CAS  PubMed  Google Scholar 

  50. Kiyasu J, Miyoshi H, Hirata A, Arakawa F, Ichikawa A, Niino D, Sugita Y, Yufu Y, Choi I, Abe Y, Uike N, Nagafuji K, Okamura T, Akashi K, Takayanagi R, Shiratsuchi M, Ohshima K (2015) Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. Blood 126:2193–2201. doi:10.1182/blood-2015-02-62960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Associazione Italiana per la Ricerca sul Cancro (to Angela Santoni), Ministero dell’Istruzione, dell’Universita’ e della Ricerca (to Gabriella Palmieri), and Sant’Andrea Onlus (to Maria Christina Cox), for financial support.

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Author notes

  1. Simone Battella and Maria Christina Cox contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Medicine, University La Sapienza, Rome, Italy

    Simone Battella & Angela Santoni

  2. Hematology Unit, AO Sant’Andrea, University La Sapienza, Via di Grottarossa 1035/1039, 00189, Rome, Italy

    M. Christina Cox & Francesca Di Landro

  3. Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161, Rome, Italy

    Raffaella La Scaleia, Lavinia Franchitti, Fabrizio Mainiero & Gabriella Palmieri

  4. Neuromed, Istituto di Ricovero e Cura a Carattere Scientifico, Pozzilli, IS, Italy

    Arianna Di Napoli & Alessandra Porzia

  5. Department of Clinical and Molecular Medicine, University La Sapienza, Rome, Italy

    Luigi Ruco & Bruno Monarca

  6. Istituto Pasteur-Fondazione Cenci Bolognetti, University La Sapienza, Rome, Italy

    Angela Santoni

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  1. Simone Battella
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Correspondence to M. Christina Cox or Gabriella Palmieri.

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Battella, S., Cox, M.C., La Scaleia, R. et al. Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy. Cancer Immunol Immunother 66, 1295–1306 (2017). https://doi.org/10.1007/s00262-017-2026-7

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