CC BY 4.0 · Rev Bras Ginecol Obstet 2021; 43(05): 368-373
DOI: 10.1055/s-0041-1730286
Original Article
Basic and translational Science/Mastology

Immunological Characteristics between αβ TDC and γδ TDC Cells in the Spleen of Breast Cancer-Induced Mice

Características imunológicas entre células TDC αβ e TDC γδ no baço de camundongos com câncer de mama induzido
1   Reseach Institute of Oncology, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
,
1   Reseach Institute of Oncology, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
2   Discipline of Immunology, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
,
1   Reseach Institute of Oncology, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
3   Department of Gynecology and Obstetrics, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
,
1   Reseach Institute of Oncology, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
3   Department of Gynecology and Obstetrics, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
› Author Affiliations
Funding The present research was supported by the National Council for Scientific and Technological Development (CNPq, in the Portuguese acronym) (grant no. 30211/2015-3), the Foundation for Education and Research of Uberaba (FUNEPU, in the Portuguese acronym) (grant no. 255/2012), the Higher Education Personnel Improvement Coordination (CAPES, in the Portuguese acronym), and the Research Support Foundation of the State of Minas Gerais (FAPEMIG, in the Portuguese acronym) (grant no. Rede 11/14).

Abstract

Objective To evaluate the antitumoral role of γδ TDC cells and αβ TDC cells in an experimental model of breast cancer.

Methods Thirty female Balb/c mice were divided into 2 groups: control group (n = 15) and induced-4T1 group (n = 15), in which the mice received 2 × 105 4T1 mammary tumor cell line. Following the 28-day experimental period, immune cells were collected from the spleen and analyzed by flow cytometry for comparison of αβ TDC (TCRαβ+ CD11c+MHCII+) and γδ TDC (TCRγδ+CD11c+MHCII+) cells regarding surface markers (CD4+ and C8+) and cytokines (IFN-γ, TNF-α, IL-12 and IL-17).

Results A total of 26.53% of γδ TDC - control group (p < 0.0001) - the proportion of αβ TDC was lower in splenic cells than γδ TDC; however, these 2 cell types were reduced in tumor conditions (p < 0.0001), and the proportion of IFN-γ, TNF-α, IL-12 and IL-17 cytokines produced by γδ TDC was higher than those produced by αβ TDC, but it decreased under conditions of tumor-related immune system response (p < 0.0001).

Conclusion Healthy mice engrafted with malignant cells 4T1 breast tumor presented TDC with γδ TCR repertoire. These cells express cytotoxic molecules of lymphocytes T, producing anti-tumor proinflammatory cytokines.

Resumo

Objetivo Esclarecer o possível papel antitumoral das células TDC γδ e TDC αβ em um modelo experimental de câncer de mama.

Métodos Trinta baços de camundongos Balb/c analisados por citometria de fluxo, separados entre grupo controle (n = 15) e o grupo tumoral induzido por 4T1 (n = 15).

Resultados Presença de 26,53% de TDC γδ nos camundongos do grupo controle (p < 0,0001), proporção de TDC αβ menor em células esplênicas do que TDC γδ; no entanto, estes dois tipos de células são reduzidos em condições tumorais (p < 0,0001), e a proporção de citocinas IFN-γ, TNF-α, IL-12 e IL-17 produzidas pelas célula TDC γδ foi maior do que as produzidas pelas células TDC αβ, mas foram diminuídas sob condições de resposta ao sistema imunológico relacionada ao tumor (p < 0,0001).

Conclusão Camundongos saudáveis induzidos ao tumor de mama 4T1 apresentaram TDC com repertório TCR γδ. Estas células expressam moléculas citotóxicas de linfócitos T, produzindo citocinas proinflamatórias anti-tumor.

Contributors

All authors were involved in the design and interpretation of the analyses, contributed with the writing of the manuscript, read, and approved the final manuscript.




Publication History

Received: 13 May 2020

Accepted: 12 February 2021

Article published online:
02 June 2021

© 2021. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 
  • References

  • 1 Kuka M, Munitic I, Ashwell JD. Identification and characterization of polyclonal αβ-T cells with dendritic cell properties. Nat Commun 2012; 3: 1223 DOI: 10.1038/ncomms2223.
  • 2 Gaulard P, Bourquelot P, Kanavaros P, Haioun C, Le Couedic JP, Divine M. et al. Expression of the alpha/beta and gamma/delta T-cell receptors in 57 cases of peripheral T-cell lymphomas. Identification of a subset of gamma/delta T-cell lymphomas. Am J Pathol 1990; 137 (03) 617-628
  • 3 Legut M, Cole DK, Sewell AK. The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy. Cell Mol Immunol 2015; 12 (06) 656-668 DOI: 10.1038/cmi.2015.28.
  • 4 Donia M, Ellebaek E, Andersen MH, Straten PT, Svane IM. Analysis of Vδ1 T cells in clinical grade melanoma-infiltrating lymphocytes. OncoImmunology 2012; 1 (08) 1297-1304 DOI: 10.4161/onci.21659.
  • 5 Wang J, Lin C, Li H, Li R, Wu Y, Liu H. et al. Tumor-infiltrating γδT cells predict prognosis and adjuvant chemotherapeutic benefit in patients with gastric cancer. OncoImmunology 2017; 6 (11) e1353858 DOI: 10.1080/2162402X.2017.1353858.
  • 6 Godder KT, Henslee-Downey PJ, Mehta J, Park BS, Chiang K-Y, Abhyankar S. et al. Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant 2007; 39 (12) 751-757 DOI: 10.1038/sj.bmt.1705650.
  • 7 Ma Y, Aymeric L, Locher C, Mattarollo SR, Delahaye NF, Pereira P. et al. Contribution of IL-17-producing γ δ T cells to the efficacy of anticancer chemotherapy. J Exp Med 2011; 208 (03) 491-503 DOI: 10.1084/jem.20100269.
  • 8 Lafont V, Sanchez F, Laprevotte E, Michaud H-A, Gros L, Eliaou J-F. et al. Plasticity of γδ T cells: impact on the anti-tumor response. Front Immunol 2014; 5: 622 DOI: 10.3389/fimmu.2014.00622.
  • 9 Davey MS, Willcox CR, Hunter S, Kasatskaya SA, Remmerswaal EBM, Salim M. et al. The human Vδ2+ T-cell compartment comprises distinct innate-like Vγ9+ and adaptive Vγ9 subsets. Nat Commun 2018; 9 (01) 1760 DOI: 10.1038/s41467-018-04076-0.
  • 10 Girardi M, Glusac E, Filler RB, Roberts SJ, Propperova I, Lewis J. et al. The distinct contributions of murine T cell receptor (TCR)gammadelta+ and TCRalphabeta+ T cells to different stages of chemically induced skin cancer. J Exp Med 2003; 198 (05) 747-755 DOI: 10.1084/jem.20021282.
  • 11 Gaafar A, Aljurf MD, Al-Sulaiman A, Iqniebi A, Manogaran PS, Mohamed GEH. et al. Defective gammadelta T-cell function and granzyme B gene polymorphism in a cohort of newly diagnosed breast cancer patients. Exp Hematol 2009; 37 (07) 838-848 DOI: 10.1016/j.exphem.2009.04.003.
  • 12 Niu C, Jin H, Li M, Xu J, Xu D, Hu J. et al. In vitro analysis of the proliferative capacity and cytotoxic effects of ex vivo induced natural killer cells, cytokine-induced killer cells, and gamma-delta T cells. BMC Immunol 2015; 16: 61 DOI: 10.1186/s12865-015-0124-x.
  • 13 Chapman NM, Chi H. Hallmarks of T-cell exit from quiescence. Cancer Immunol Res 2018; 6 (05) 502-508 DOI: 10.1158/2326-6066.CIR-17-0605.
  • 14 Ferrarini M, Ferrero E, Dagna L, Poggi A, Zocchi MR. Human gammadelta T cells: a nonredundant system in the immune-surveillance against cancer. Trends Immunol 2002; 23 (01) 14-18 DOI: 10.1016/s1471-4906(01)02110-x.
  • 15 Street SEA, Hayakawa Y, Zhan Y, Lew AM, MacGregor D, Jamieson AM. et al. Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cells. J Exp Med 2004; 199 (06) 879-884 DOI: 10.1084/jem.20031981.
  • 16 Liu Z, Eltoum IEA, Guo B, Beck BH, Cloud GA, Lopez RD. Protective immunosurveillance and therapeutic antitumor activity of gammadelta T cells demonstrated in a mouse model of prostate cancer. J Immunol 2008; 180 (09) 6044-6053 DOI: 10.4049/jimmunol.180.9.6044.
  • 17 Lança T, Costa MF, Gonçalves-Sousa N, Rei M, Grosso AR, Penido C. et al. Protective role of the inflammatory CCR2/CCL2 chemokine pathway through recruitment of type 1 cytotoxic γδ T lymphocytes to tumor beds. J Immunol 2013; 190 (12) 6673-6680 DOI: 10.4049/jimmunol.1300434.
  • 18 Born WK, Reardon CL, O'Brien RL. The function of gammadelta T cells in innate immunity. Curr Opin Immunol 2006; 18 (01) 31-38 DOI: 10.1016/j.coi.2005.11.007.
  • 19 Yang Y, Xu C, Wu D, Wang Z, Wu P, Li L. et al. γδ T cells: crosstalk between microbiota, chronic inflammation, and colorectal cancer. Front Immunol 2018; 9: 1483 DOI: 10.3389/fimmu.2018.0148.
  • 20 Zhao Y, Niu C, Cui J. Gamma-delta (γδ) T cells: friend or foe in cancer development?. J Transl Med 2018; 16 (01) 3 DOI: 10.1186/s12967-017-1378-2.
  • 21 Wu P, Wu D, Ni C, Ye J, Chen W, Hu G. et al. γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Immunity 2014; 40 (05) 785-800 DOI: 10.1016/j.immuni.2014.03.013.
  • 22 Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng WO, Kim D. et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med 2015; 21 (08) 938-945 DOI: 10.1038/nm.3909.
  • 23 Gao Y, Yang W, Pan M, Scully E, Girardi M, Augenlicht LH. et al. γ δ T cells provide an early source of interferon γ in tumor immunity. J Exp Med 2003; 198 (03) 433-442 DOI: 10.1084/jem.20030584.
  • 24 He W, Hao J, Dong S, Gao Y, Tao J, Chi H. et al. Naturally activated V γ 4 γ δ T cells play a protective role in tumor immunity through expression of eomesodermin. J Immunol 2010; 185 (01) 126-133 DOI: 10.4049/jimmunol.0903767.
  • 25 Sebestyen Z, Prinz I, Déchanet-Merville J, Silva-Santos B, Kuball J. Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies. Nat Rev Drug Discov 2020; 19 (03) 169-184 DOI: 10.1038/s41573-019-0038-z.
  • 26 Dieli F, Vermijlen D, Fulfaro F, Caccamo N, Meraviglina S, Cicero G. et al. Targeting human γδ T cells with zoledronate and interleukin-2 for immunotherapy of hormone-refractory prostate cancer. Cancer Res 2007; 67 (15) 7450-7457 DOI: 10.1158/0008-5472.CAN-07-0199.
  • 27 Poccia F, Gioia C, Martini F, Sacchi A, Piacentini P, Tempestilli M. et al. Zoledronic acid and interleukin-2 treatment improves immunocompetence in HIV-infected persons by activating Vgamma9Vdelta2 T cells. AIDS 2009; 23 (05) 555-565 DOI: 10.1097/QAD.0b013e3283244619.