medigraphic.com
ISSN 1561-2996 (Digital)
ISSN 0864-0289 (Impreso)

2020, Número 2

<< Anterior Siguiente >>

Rev Cubana Hematol Inmunol Hemoter 2020; 36 (2)


Caracterización de los inmunofenotipos linfocitarios de sangre periférica en pacientes con cáncer

Arango PMC, Villegas VCA, Soto PP, Torres LG, Morejón MA, Faxas GME

Idioma: Español
Referencias bibliográficas: 45
Paginas: 1-19
Archivo PDF: 704.86 Kb.


RESUMEN

Introducción: La determinación de los inmunofenotipos linfocitarios en sangre periférica forma parte de la evaluación del estado general del sistema inmunitario. Estos exámenes ofrecen informaciones sobre la distribución, concentración y funcionabilidad de las células inmunitarias, lo cual contribuye a establecer pronósticos en el cáncer y predicciones a las respuestas terapéuticas.
Objetivo: Evaluar la distribución de las concentraciones linfocitarias circulantes en sangre periférica de pacientes con cáncer.
Métodos: Se realizó un estudio analítico en 154 pacientes con cáncer, atendidos en el Instituto de Oncología y Radiobiología de La Habana, durante los años 2017 a 2019. Se empleó la citometría de flujo multiparamétrica para identificar los inmunofenotipos linfocitarios. Este procedimiento se realizó antes de comenzar cualquier tratamiento inmunoterapéutico.
Resultados: Los pacientes con cáncer mostraron mayor heterogeneidad en la distribución de las poblaciones linfocitarias respecto a los controles. En los pacientes la mediana de los linfocitos totales y de las subpoblaciones linfocitarias CD3+, CD4+, CD8+ y CD19+ fueron significativamente menores. Los linfocitos T dobles positivos (CD4/CD8) se encontraron elevados significativamente. No se hallaron diferencias entre sexos. La edad se asoció negativamente con las concentraciones de las poblaciones T en tumores sólidos, y con T y B en los linfomas. En el cáncer de próstata se obtuvieron los valores más bajos de poblaciones linfocitarias.
Conclusiones: Los pacientes con cáncer tienen menor concentración de linfocitos en sangre periférica que los controles sanos. Las células más afectadas fueron las subpoblaciones T y los linfocitos B. La edad se asoció negativamente con las concentraciones sanguíneas de linfocitos, lo cual pudiera estar en relación con la inmunosenescencia.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN estimates of Incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin 2018;68:394-424.

  2. MINSAP. Anuario estadístico de salud, 2017. La Habana: MINSAP; 2018[acceso 06/01/2020]. Disponible en: Disponible en: http://www.sld.cu/sitios/dne

  3. Blank CU, Haanen JB, Ribas A, Schumacher TN. Cancer immunology. The "cancer immunogram". Science 2016;352:658-60.

  4. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321-30.

  5. Shukuya T, Carbone DP. Predictive markers for the efficacy of anti-PD-1/PD-L1 antibodies in lung cancer. J Thorac Oncol. 2016;11:976-88.

  6. Fridman WH, Zitvogel L, Sautès-Fridman C. Kroemer G. The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol 2017;14:717-34.

  7. Ye L, Zhang F, Li H, Yang L, Lv T, Gu W, et al. Circulating tumor cells were associated with the number of T lymphocyte subsets and NK cells in peripheral blood in advanced non-small-cell lung cancer. Dis Markers. 2017;2017:5727815

  8. Iwahori K, Shintani Y, Funaki S, Yamamoto Y, Matsumoto M, Yoshida T. Peripheral T cell cytotoxicity predicts T cell function in the tumor microenvironment. Sci Rep. 2019;9:2636.

  9. Liang H, Chu X, Zhao J, Xing G, Si Y. Elevated peripheral blood B lymphocytes and CD3+CD4-CD8- T lymphocytes in patients with non-small cell lung cancer: A preliminary study on peripheral immune profile. Oncol Let. 2018;15:8387-95.

  10. Swartz MA, Iida N, Yull FE, Roberts EW, Sangaletti S, Wong MH, et al. Tumor microenvironment complexity: Emerging roles in cancer therapy. Cancer Res. 2012; 72:2473-80.

  11. Lin L, Hu X, Zhang H and Hu H. Tertiary Lymphoid Organs in Cancer Immunology: Mechanisms and the New Strategy for Immunotherapy. Front Immunol. 2019;10:1398.

  12. Colbeck EJ, Ager A, Gallimore A, Jones GW. Tertiary Lymphoid Structures in Cancer: Drivers of Antitumor Immunity, Immunosuppression, or Bystander Sentinels in Disease? Front Immunol. 2017;8:1830.

  13. Andrea Cossarizza, Chang HD, Radbruch A, Akdis M, Andra I, Annunziato F,et al. Guidelines for the use of flow cytometry and cell sorting in immunological studies. Eur J Immunol. 2017;47:1584-797.

  14. Rudolf RCM, Gonçalves KT, Martignago ML, Mengatto V, Gaspar PC, Rabello AC, et al. Determination of lymphocyte subset reference ranges in peripheral blood of healthy adults by a dual-platform flow cytometry method. Immunol Let. 2015;163:96-101.

  15. Gadalla R, Noamani B, MacLeod BL, Dickson RJ, Guo M, Xu W, et al. Validation of CyTOF against flow cytometry for immunological studies and monitoring of human cancer clinical trials. Front Oncol. 2019;9:415.

  16. Scott GD, Atwater SK, Gratzinger DA. Normative data for flow cytometry immunophenotyping of benign lymph nodes sampled by surgical biopsy. J Clin Pathol. 2017;0:1-6.

  17. Stabile H, Fionda C, Gismondi A, Santoni A. Role of Distinct Natural Killer Cell Subsets in Anticancer Response. Front Immunol. 2017;8:293.

  18. Desfrançois J, Moreau-Aubry A, Vignard V, Godet Y, Khammari A, Dréno B, et al. Double Positive CD4CD8 aß T Cells: A New Tumor-Reactive Population in Human Melanomas. Plos One. 2010;5(1):e8437.

  19. Kokuina E, Breff C, Villegas CA, Mora-Díaz I. Normal values of T, B and NK lymphocytes subpopulations in peripheral blood of healthy Cuban adults. MEDICC Review 2019; 21(2-3):16-21.

  20. Villegas CA, Kokuina E, Breff MC. Estimating Normal Values of Rare T-lymphocyte Populations in Peripheral Blood of Healthy Cuban Adults. MEDICC Review. 2018;20(4):20-6.

  21. Ahmad SS, Akhtar K, Verma AK, Mallik AZ and Siddiqui SA: Total peripheral lymphocyte count in malignant tumors: An index of prognostication. J Med Sci. 2012;12:24-8.

  22. Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, et al: Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69:5383-91.

  23. Batty N, Ghonimi E, Feng L, Fayad L, Younes A, Rodriguez MA, et al. The absolute monocyte and lymphocyte prognostic index for patients with diffuse large B-cell lymphoma who receive R-CHOP. Clin Lymphoma Myeloma Leuk. 2013;13(1):5-18.

  24. Feng Z, Wen H, Bi R, Ju X, Chen X, Yang W, et al. Preoperative Neutrophil-to-Lymphocyte Ratio as a predictive and prognostic factor for high-grade serous ovarian cancer. Plos One. 2016;11(5):e0156101.

  25. Yang X, Ren H, Sun Y, Shao Y, Zhang L, Li H, et al. Prognostic significance of CD4/CD8 ratio in patients with breast cancer. Int J Clin Exp Pathol. 2017;10(4):4787-93.

  26. Dewyer NA, Wolf GT, Light E, Worden F, Urba S, Eisbruch A, et al. Circulating CD4-positive lymphocyte levels predict response to induction chemotherapy in patients with advanced laryngeal cancer. Head Neck. 2014;36(1):9-14.

  27. Hagland HR, Lea D, Watson MM, Søreide K. Correlation of blood T-Cells to intratumoural density and location of CD3+ and CD8+ T-Cells in colorectal cancer. Anticancer Res. 2017;37:675-84.

  28. Guo F, Cui JW. The Role of Tumor-Infiltrating B Cells in Tumor Immunity. J Oncol. 2019 Sep;2019:2592419. doi: 10.1155/2019/2592419

  29. Sarvaria J, Madrigal A, Saudemont A. B cell regulation in cancer and anti-tumor immunity. Cel Mol Immunol. 2017;14:662-674.

  30. Zhang-Ru Y, Ning Z, Jin M, Ze-Liang S, Bing-Xin L, Xian-Wei W, et al. Peripheral lymphocyte subset variation predicts prostate cancer carbon ion radiotherapy outcomes. Oncotarget. 2019;7(18):26422-35.

  31. Matsuzaki J, Tsuji T, Chodon T, Ryan C, Koya RC, Odunsi K. Rare population of tumor antigen-specific CD4+CD8+ double-positive aß T lymphocytes uniquely provide CD8-independent TCR genes for engineering therapeutic T cells. J Immunother Cancer. 2019;7(7):1-18.

  32. Menard LC, Fischer P, Kakrecha B, Linsley PS, Wambre E, Liu MC, et al. Renal Cell Carcinoma (RCC) tumors display large expansion of double positive (DP) CD4+CD8+ T Cells with expression of exhaustion markers. Front Immunol. 2018;9:2728.

  33. Bohner P, Chevalier MF, Cesson V, Rodrigues-Dias S-C, Dartiguenave F, Burruni R, et al. Double Positive CD4+CD8+ T cells are enriched in urological cancers and favor T Helper-2 polarization. Front Immunol. 2019;10:622.

  34. Wu D, Thomas A, Fromm JR. Reactive T cells by flow cytometry distinguish Hodgkin lymphomas from T Cell/Histiocyte-Rich Large B Cell Lymphoma. Cytometry Part B. 2016;90B:424-32.

  35. Voelkl S, Gary R, Mackensen A. Characterization of the immunoregulatory function of human TCR-aß+ CD4-CD8- double-negative T cells. Eur J Immunol. 2011;41:739-48.

  36. Young KJ, Kay LS, Phillips MJ, Zhang L. Antitumor activity mediated by double-negative T cells. Cancer Res. 2003;63:8014-21.

  37. Lee J, Minden MD, Chen WC, Streck E, Chen B, Kang H, et al. Allogeneic human double negative T cells as a novel immunotherapy for acute myeloid leukemia and its underlying mechanisms. Clin Cancer Res. 2018;24:370-82.

  38. Lu Y, Hu P, Zhou H, Yang Z, Sun Y, Hoffman RM, et al. Double-negative T cells inhibit proliferation and invasion of human pancreatic cancer cells in co-culture. Anticancer Res. 2019;39:5911-18.

  39. Yao J, Ly D, Dervovic D, Fang L, Lee JB, Kang H, et al. Human double negative T cells target lung cancer via ligand-dependent mechanisms that can be enhanced by IL-15. J Immunother Cancer. 2019;7:17.

  40. Bae EA, Seo H, Kim BS, Choi J, Jeon I, Shin KS, et al. Activation of NKT cells in an anti-PD-1-resistant tumor model enhances antitumor immunity by reinvigorating exhausted CD8 T cells. Cancer Res. 2018;78:5315-26.

  41. Paul S, Chhatar S, Mishra A, Lal G. Natural killer T cell activation increases iNOS+CD206- M1 macrophage and controls the growth of solid tumor. J Immunother Cancer. 2019;7:208.

  42. Lin CY, Kwon H, Rangel GO, Li X, Chung D, Li Z.Sex differences in using systemic inflammatory markers to prognosticate patients with head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2018;27:1176-85.

  43. Michel JJ, Griffin P, Vallejo AN. Functionally diverse NK-Like T Cells are effectors and predictors of successful aging. Front Immunol. 2016;7:530.

  44. Wang J, Yang G, Wang D, Liu K, Ma Y, Liu H, et al. Changes of peripheral lymphocyte subsets and cytokine environment during aging and deteriorating gastrointestinal tract health status. Oncotarget. 2017;8(37):60764-77.

  45. Palmera S, Albergantea L, Blackburnd CC, Newmana TJ. Thymic involution and rising disease incidence with age. Proc Natl Acad Sci USA. 2018 Feb 20;115(8):1883-8. doi: 10.1073/pnas.1714478115.




2020     |     www.medigraphic.com