Systemic immune response associated with radiation therapy in B‑cell non‑Hodgkin's lymphoma of Waldeyer's ring

Niu,Xingjian; Ji,Hongfei; Wang,Yiran; Hu,Songliu; Xuan,Qijia; Huang,Lan; Yin,Lei; Su,Wenjia; Li,Liru; Zhang,Han; Li,Jingtong; Yang,Yue; An,Weiwei; Zhang,Qingyuan

doi:10.3892/or.2018.6748

Systemic immune response associated with radiation therapy in B‑cell non‑Hodgkin's lymphoma of Waldeyer's ring

Authors:
- Xingjian Niu
- Hongfei Ji
- Yiran Wang
- Songliu Hu
- Qijia Xuan
- Lan Huang
- Lei Yin
- Wenjia Su
- Liru Li
- Han Zhang
- Jingtong Li
- Yue Yang
- Weiwei An
- Qingyuan Zhang
View Affiliations

Affiliations: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China, Institute of Cancer Prevention and Treatment, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China, Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, Precision Medicine Center, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
Published online on: September 28, 2018 https://doi.org/10.3892/or.2018.6748
Pages: 3674-3684

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Radiation therapy (RT) is one of the most effective therapeutic modalities for B‑cell non‑Hodgkin's lymphoma of Waldeyer's ring (WR‑B‑NHL). However, the responsiveness of RT remains controversial and clinical biomarkers are required to predict survival in RT‑treated patients with WR‑B‑NHL. Previous studies have suggested an association between RT and systemic immune responses. In the present retrospective study, the lymphocyte to monocyte ratio (LMR) was identified as a systemic immune indicator in RT‑treated patients with WR‑B‑NHL, and the prognostic value of the LMR with RT and systemic immune responses were evaluated. The optimal cut‑off value of the LMR was selected as 3.14, and a high LMR demonstrated improved prognosis and was considered an independent prognostic indicator in RT‑treated patients, particularly in patients with distant non‑irradiated lesions. Furthermore, reverse transcription‑quantitative polymerase chain reaction and ELISA analysis of irradiated lymphoma cell lines and serum samples from patients with WR‑B‑NHL demonstrated the upregulated expression levels of 4‑1BB ligands, calreticulin and high mobility group box 1 compared with non‑irradiated groups. Additionally, CD8+ T cells and expression levels of interferon‑γ in T cells co‑cultured with irradiated cells were significantly increased compared with non‑irradiated cells. The results indicated that the anti‑programmed cell death protein 1 (PD‑1) antibody may serve a role in lymphoma therapy when combined with RT. The results of the present study demonstrated the prognostic significance of the LMR associated with RT in patients with WR‑B‑NHL and acknowledged the potential use of PD‑1 antibody in RT‑treated lymphomas.

View Figures

View References

1	Armitage JO, Gascoyne RD, Lunning MA and Cavalli F: Non-Hodgkin lymphoma. Lancet. 390:298–310. 2017. View Article : Google Scholar : PubMed/NCBI
2	Qi SN, Li YX, Wang H, Wang WH, Jin J, Song YW, Wang SL, Liu YP, Zhou LQ and Yu ZH: Diffuse large B-cell lymphoma: Clinical characterization and prognosis of Waldeyer ring versus lymph node presentation. Cancer. 115:4980–4989. 2009. View Article : Google Scholar : PubMed/NCBI
3	Wu RY, Li YX, Wang WH, Jin J, Wang SL, Liu YP, Song YW, Fang H, Ren H, Liu QF, et al: Clinical disparity and favorable prognoses for patients with Waldeyer ring extranodal nasal-type NK/T-cell lymphoma and diffuse large B-cell lymphoma. Am J Clin Oncol. 37:41–46. 2014. View Article : Google Scholar : PubMed/NCBI
4	Xu YG, Qi SN, Wang SL, Liu YP, Wang WH, Jin J, Song YW, Ren H, Fang H, He XH, et al: Dosimetric and clinical outcomes with intensity modulated radiation therapy after chemotherapy for patients with early-stage diffuse large B-cell lymphoma of Waldeyer ring. Int J Radiat Oncol Biol Phys. 96:379–386. 2016. View Article : Google Scholar : PubMed/NCBI
5	Phan J, Mazloom A, Medeiros LJ, Zreik TG, Wogan C, Shihadeh F, Rodriguez MA, Fayad L, Fowler N, Reed V, et al: Benefit of consolidative radiation therapy in patients with diffuse large B-cell lymphoma treated with R-CHOP chemotherapy. J Clin Oncol. 28:4170–4176. 2010. View Article : Google Scholar : PubMed/NCBI
6	Moser EC, Kluin-Nelemans HC, Carde P, Meerwaldt JH, Tirelli U, Aleman BM, Baars J, Thomas J, van Glabbeke M and Noordijk EM: Impact of involved field radiotherapy in partial response after doxorubicin-based chemotherapy for advanced aggressive non-Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys. 66:1168–1177. 2006. View Article : Google Scholar : PubMed/NCBI
7	Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM and Glick JH: Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 22:3032–3038. 2004. View Article : Google Scholar : PubMed/NCBI
8	Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, et al: CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: A study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 25:787–792. 2007. View Article : Google Scholar : PubMed/NCBI
9	Franceschini D, Franzese C, Navarria P, Ascolese AM, De Rose F, Del Vecchio M, Santoro A and Scorsetti M: Radiotherapy and immunotherapy: Can this combination change the prognosis of patients with melanoma brain metastases? Cancer Treat Rev. 50:1–8. 2016. View Article : Google Scholar : PubMed/NCBI
10	Yoshimoto Y, Suzuki Y, Mimura K, Ando K, Oike T, Sato H, Okonogi N, Maruyama T, Izawa S, Noda SE, et al: Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model. PLoS One. 9:e925722014. View Article : Google Scholar : PubMed/NCBI
11	Herrera FG, Bourhis J and Coukos G: Radiotherapy combination opportunities leveraging immunity for the next oncology practice. CA Cancer J Clin. 67:65–85. 2017. View Article : Google Scholar : PubMed/NCBI
12	Weichselbaum RR, Liang H, Deng L and Fu YX: Radiotherapy and immunotherapy: A beneficial liaison? Nat Rev Clin Oncol. 14:365–379. 2017. View Article : Google Scholar : PubMed/NCBI
13	Galluzzi L, Kepp O and Kroemer G: Immunogenic cell death in radiation therapy. Oncoimmunology. 2:e265362013. View Article : Google Scholar : PubMed/NCBI
14	Bloy N, Pol J, Manic G, Vitale I, Eggermont A, Galon J, Tartour E, Zitvogel L, Kroemer G and Galluzzi L: Trial Watch: Radioimmunotherapy for oncological indications. Oncoimmunology. 3:e9549292014. View Article : Google Scholar : PubMed/NCBI
15	Surace L, Lysenko V, Fontana AO, Cecconi V, Janssen H, Bicvic A, Okoniewski M, Pruschy M, Dummer R, Neefjes J, et al: Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response. Immunity. 42:767–777. 2015. View Article : Google Scholar : PubMed/NCBI
16	Kroemer G, Galluzzi L, Kepp O and Zitvogel L: Immunogenic cell death in cancer therapy. Annu Rev Immunol. 31:51–72. 2013. View Article : Google Scholar : PubMed/NCBI
17	Ebner DK, Tinganelli W, Helm A, Bisio A, Yamada S, Kamada T, Shimokawa T and Durante M: The immunoregulatory potential of particle radiation in cancer therapy. Front Immunol. 8:992017. View Article : Google Scholar : PubMed/NCBI
18	Demaria S, Golden EB and Formenti SC: Role of local radiation therapy in cancer immunotherapy. JAMA Oncol. 1:1325–1332. 2015. View Article : Google Scholar : PubMed/NCBI
19	Shibutani M, Maeda K, Nagahara H, Iseki Y, Ikeya T and Hirakawa K: Prognostic significance of the preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer. Oncol Lett. 13:1000–1006. 2017. View Article : Google Scholar : PubMed/NCBI
20	Ji H, Xuan Q, Yan C, Liu T, Nanding A and Zhang Q: The prognostic and predictive value of the lymphocyte to monocyte ratio in luminal-type breast cancer patients treated with CEF chemotherapy. Oncotarget. 7:34881–34889. 2016. View Article : Google Scholar : PubMed/NCBI
21	Eo WK, Chang HJ, Kwon SH, Koh SB, Kim YO, Ji YI, Kim HB, Lee JY, Suh DS, Kim KH, et al: The lymphocyte-monocyte ratio predicts patient survival and aggressiveness of ovarian cancer. J Cancer. 7:289–296. 2016. View Article : Google Scholar : PubMed/NCBI
22	Marconato L, Martini V, Stefanello D, Moretti P, Ferrari R, Comazzi S, Laganga P, Riondato F and Aresu L: Peripheral blood lymphocyte/monocyte ratio as a useful prognostic factor in dogs with diffuse large B-cell lymphoma receiving chemoimmunotherapy. Vet J. 206:226–230. 2015. View Article : Google Scholar : PubMed/NCBI
23	Wang L, Wang H, Xia ZJ, Huang HQ, Jiang WQ, Lin TY and Lu Y: Peripheral blood lymphocyte to monocyte ratio identifies high-risk adult patients with sporadic Burkitt lymphoma. Ann Hematol. 94:1645–1654. 2015. View Article : Google Scholar : PubMed/NCBI
24	Ji H, Niu X, Yin L, Wang Y, Huang L, Xuan Q, Li L, Zhang H, Li J, Yang Y, et al: Ratio of immune response to tumor burden predicts survival via regulating functions of lymphocytes and monocytes in diffuse large B-cell lymphoma. Cell Physiol Biochem. 45:951–961. 2018. View Article : Google Scholar : PubMed/NCBI
25	Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H and Jaffe ES: The 2008 WHO classification of lymphoid neoplasms and beyond: Evolving concepts and practical applications. Blood. 117:5019–5132. 2011. View Article : Google Scholar : PubMed/NCBI
26	Cassidy RJ, Jegadeesh N, Switchenko J, Danish H, Esiashvili N, Flowers CR and Khan MK: The role of radiotherapy for patients over age 60 with diffuse large B-cell lymphoma in the rituximab era. Leuk Lymphoma. 57:1876–1882. 2016. View Article : Google Scholar : PubMed/NCBI
27	Lee ST, Liu S, Radvanyi L, Sukhumalchandra P, Molldrem JJ, Wieder ED, Hwu P, Liu YJ, Kwak LW, Lizée G and Neelapu SS: A novel strategy for rapid and efficient isolation of human tumor-specific CD4⁺ and CD8⁺ T-cell clones. J Immunol Methods. 331:13–26. 2008. View Article : Google Scholar : PubMed/NCBI
28	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔC^T method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
29	Sharabi AB, Lim M, DeWeese TL and Drake CG: Radiation and checkpoint blockade immunotherapy: Radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 16:e498–e509. 2015. View Article : Google Scholar : PubMed/NCBI
30	Zhou S, Xu L, Ma Y, Tang L, Zhang Y, Shi Y, Sun L, Chen Y, Liang B, Zhou Y, et al: Peripheral blood lymphocyte to monocyte ratio recovery from low levels at diagnosis after completion of first line therapy predicts good clinical outcomes in patients with diffuse large B-cell lymphoma. Oncotarget. 8:19556–19565. 2017.PubMed/NCBI
31	Ho CL, Lu CS, Chen JH, Chen YG, Huang TC and Wu YY: Neutrophil/Lymphocyte Ratio, Lymphocyte/Monocyte Ratio, and Absolute Lymphocyte Count/Absolute monocyte count prognostic score in diffuse large B-cell lymphoma: Useful prognostic tools in the rituximab era. Medicine. 94:e9932015. View Article : Google Scholar : PubMed/NCBI
32	Jia T, Zhang R, Zhu HY, Liang JH, Wang L, Wu W, Cao L, Li JY and Xu W: Prognostic significance of peripheral blood absolute monocyte count and lymphocyte to monocyte ratio in anaplastic large cell lymphoma. Cancer Biomark. Jun 12–2018.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
33	Mantovani A, Allavena P, Sica A and Balkwill F: Cancer-related inflammation. Nature. 454:436–444. 2008. View Article : Google Scholar : PubMed/NCBI
34	Shibutani M, Maeda K, Nagahara H, Ohtani H, Sakurai K, Yamazoe S, Kimura K, Toyokawa T, Amano R, Tanaka H, et al: Prognostic significance of the lymphocyte-to-monocyte ratio in patients with metastatic colorectal cancer. World J Gastroenterol. 21:9966–9973. 2015. View Article : Google Scholar : PubMed/NCBI
35	Noy R and Pollard JW: Tumor-associated macrophages: From mechanisms to therapy. Immunity. 41:49–61. 2014. View Article : Google Scholar : PubMed/NCBI
36	Quail DF and Joyce JA: Microenvironmental regulation of tumor progression and metastasis. Nat Med. 19:1423–1437. 2013. View Article : Google Scholar : PubMed/NCBI
37	Lin GN, Liu PP, Liu DY, Peng JW, Xiao JJ and Xia ZJ: Prognostic significance of the pre-chemotherapy lymphocyte-to-monocyte ratio in patients with previously untreated metastatic colorectal cancer receiving FOLFOX chemotherapy. Chin J Cancer. 35:52016. View Article : Google Scholar : PubMed/NCBI
38	Luo H, Ge H, Cui Y, Zhang J, Fan R, Zheng A, Zheng X and Sun Y: Systemic inflammation biomarkers predict survival in patients of early stage Non-small cell lung cancer treated with stereotactic ablative radiotherapy-a single center experience. J Cancer. 9:182–188. 2018. View Article : Google Scholar : PubMed/NCBI
39	Dovedi SJ, Lipowska-Bhalla G, Beers SA, Cheadle EJ, Mu L, Glennie MJ, Illidge TM and Honeychurch J: Antitumor efficacy of radiation plus immunotherapy depends upon dendritic cell activation of effector CD8⁺ T cells. Cancer Immunol Res. 4:621–630. 2016. View Article : Google Scholar : PubMed/NCBI
40	Golden EB, Chhabra A, Chachoua A, Adams S, Donach M, Fenton-Kerimian M, Friedman K, Ponzo F, Babb JS, Goldberg J, et al: Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: A proof-of-principle trial. Lancet Oncol. 16:795–803. 2015. View Article : Google Scholar : PubMed/NCBI
41	Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, et al: Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 366:925–931. 2012. View Article : Google Scholar : PubMed/NCBI
42	Kumari A and Garnett-Benson C: Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade. BMC Res Notes. 9:922016. View Article : Google Scholar : PubMed/NCBI
43	de Winde CM, Elfrink S and van Spriel AB: Novel insights into membrane targeting of B cell lymphoma. Trends Cancer. 3:442–453. 2017. View Article : Google Scholar : PubMed/NCBI
44	Jelinek T, Mihalyova J, Kascak M, Duras J and Hajek R: PD-1/PD-L1 inhibitors in haematological malignancies: Update 2017. Immunology. 152:357–371. 2017. View Article : Google Scholar : PubMed/NCBI
45	Mitteldorf C, Berisha A, Pfaltz MC, Broekaert SMC, Schön MP, Kerl K and Kempf W: Tumor microenvironment and checkpoint molecules in primary cutaneous diffuse large B-cell lymphoma-new therapeutic targets. Am J Surg Pathol. 41:998–1004. 2017. View Article : Google Scholar : PubMed/NCBI
46	Boussiotis VA, Chatterjee P and Li L: Biochemical signaling of pd-1 on T cells and its functional implications. Cancer J. 20:265–271. 2014. View Article : Google Scholar : PubMed/NCBI
47	Nemoto Y, Shosu K, Okuda M, Noguchi S and Mizuno T: Development and characterization of monoclonal antibodies against canine PD-1 and PD-L1. Vet Immunol Immunopathol. 198:19–25. 2018. View Article : Google Scholar : PubMed/NCBI