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CD3ζ Expression and T Cell Proliferation are Inhibited by TGF-β1 and IL-10 in Cervical Cancer Patients

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Abstract

Introduction

Cervical cancer development from a squamous intraepithelial lesion is thought to be favored by an impaired T cell immunity. We evaluated parameters of T cell alterations such as proliferation, cytokine, and CD3ζ expression in peripheral blood and tumor-infiltrating T lymphocytes from women with squamous intraepithelial lesions (SIL) or cervical cancer (CC).

Results and Discussion

T cell proliferation and cytokine messenger RNA (mRNA) expression were similar in women with SIL and healthy donors, whereas low T cell proliferation and lower mRNA expression of IL-2, IL-10 and IFN-γ were observed in women with CC. Moreover, infiltrating cells showed marginal responses. We also found that CD3ζ mRNA expression, whose protein is required for T cell activation, correlated with a decreased proliferation in advanced stages of the disease.

Conclusion

Experiments with T cells from healthy donors in the presence TGF-β1 or IL-10 suggest that these cytokines have a relevant role in T cell responses during CC progression.

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Acknowledgments

We are grateful to the volunteers participating in this study as well as the staff of the Departments of Pathology and Surgery from the general hospitals. We also appreciate the kindness of Dr. Celso Ramos (INSP) and Dr. Raúl Barrera (INER) for sharing some instruments for the proliferation technique; the willingness to share some technical tips for TIL isolation of Dr. Llorente (INNSSZ); and the technical advice of Milena Saki and Hector Maldonado (INNSSZ), Patricia Rojo and Gibrán Pérez (Dr. Morenos’s lab), and Carla Olvia (INSP). This work was supported by the Instituto Nacional de Salud Pública in Mexico and grants from CONACYT-SEP 49574-24483-M, Mexico. C.E. Díaz Benítez was a recipient of a fellowship from CONACYT. This work was submitted in partial fulfillment of the requirements for the PhD. degree of Díaz Benítez C. E. from the Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico.

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Authors and Affiliations

  1. División de Infecciones Crónicas y Cáncer, Instituto Nacional de Salud Pública de México, Avenida Universidad #655, Sta. María Ahuacatitlán, 62508, Cuernavaca, Morelos, Mexico

    Cinthya E. Díaz-Benítez, Karla R. Navarro-Fuentes, Jacqueline A. Flores-Sosa, Janet Juárez-Díaz, Felipe J. Uribe-Salas, Alfredo Lagunas-Martínez, Victor H. Bermúdez-Morales, Jesús Martínez-Barnetche & Vicente Madrid-Marina

  2. Departamento de Oncología y División de Patología, Hospital General, Mexico City, Mexico

    Edgar Román-Basaure, Ludwig E. González-Mena & Patricia Alonso de Ruíz

  3. Departamento de Displasias, Hospital General Parres, Cuernavaca, Mexico

    Guillermina López-Estrada

  4. Instituto de Immunología y Virología, Universidad Autónoma de Nuevo León, Monterrey, Mexico

    Juan M. Alcocer-González

  5. Laboratorio de Patología Experimental, Departamento de Patología, Instituto Nacional de Medicina y Nutrición “Salvador Zubirán”, Mexico City, Mexico

    Rogelio Hernández-Pando

  6. Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico

    Yvonne Rosenstein

  7. Unidad de Investigación en Enfermedades autoinmunes, División de Infecciones Crónicas y Cáncer, Instituto Nacional de Salud Pública de México, Mexico City, Mexico

    José Moreno

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  1. Cinthya E. Díaz-Benítez
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  2. Karla R. Navarro-Fuentes
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  3. Jacqueline A. Flores-Sosa
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  16. José Moreno
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  17. Vicente Madrid-Marina
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Correspondence to Vicente Madrid-Marina.

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Díaz-Benítez, C.E., Navarro-Fuentes, K.R., Flores-Sosa, J.A. et al. CD3ζ Expression and T Cell Proliferation are Inhibited by TGF-β1 and IL-10 in Cervical Cancer Patients. J Clin Immunol 29, 532–544 (2009). https://doi.org/10.1007/s10875-009-9279-7

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