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Immune checkpoint expression on peripheral lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis
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  • Fabiola Solorzano Ibarra ,
  • Alan Alejandre González ,
  • Pablo Ortiz Lazareno ,
  • Blanca Bastidas Ramirez,
  • Abraham Zepeda Moreno,
  • Martha Téllez Bañuelos,
  • Nehla Banu,
  • Oscar Carrillo Garibaldi ,
  • Arturo Chavira Alvarado ,
  • Miriam Bueno Topete,
  • Susana del Toro Arreola,
  • Jesse Haramati
Fabiola Solorzano Ibarra
Instituto de Enfermedades Crónico Degenerativas, CUCS, Universidad de Guadalajara
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Alan Alejandre González
Instituto de Enfermedades Crónico Degenerativas, CUCS, Universidad de Guadalajara
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Pablo Ortiz Lazareno
Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social
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Blanca Bastidas Ramirez
Instituto de Enfermedades Crónico Degenerativas, CUCS, Universidad de Guadalajara
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Abraham Zepeda Moreno
Instituto de Investigación en Cáncer en la Infancia y Adolescencia, CUCS, Universidad de Guadalajara
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Martha Téllez Bañuelos
Laboratorio de Inmunobiología, CUCBA, Universidad de Guadalajara
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Nehla Banu
Instituto de Enfermedades Crónico Degenerativas, CUCS, Universidad de Guadalajara
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Oscar Carrillo Garibaldi
Clínica de Tumores Pélvicos, Instituto Jalisciense de Cancerología, Organismo Público Descentralizado
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Arturo Chavira Alvarado
Nuevo Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”
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Miriam Bueno Topete
Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara
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Susana del Toro Arreola
Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara
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Jesse Haramati
Universidad de Guadalajara Centro Universitario de Ciencias Biologicas y Agropecuarias
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Abstract

Abstract In recent years, immune checkpoint therapy to reverse NK and T cell exhaustion has emerged as a promising treatment in various cancers. Recently, the FDA has approved anti-PD-1 pembrolizumab for patients with recurrent or metastatic cervical cancer. Other checkpoint molecules, such as TIGIT and Tim-3 have yet to be fully explored in this disease. Here, we found that PD-1, TIGIT, and Tim-3 are over-expressed on some peripheral blood CD56dim and CD56bright NK cells and T cells in cervical cancer patients and women with premalignant lesions. However, we observed stronger significance and separation between groups when these three molecules were examined together. These cells, with an apparently “exhausted” phenotype, were significantly augmented in patients. Different PD-1 levels (PD1low, PD1int, PD-1hi) on T cells were used to further define checkpoint positive populations. Soluble PD-L1 was observed to be increased in cervical cancer. Within the cancer group, the highest levels of sPD-L1 and triple positive or double positive cells and tumor stage were found similarly within tumors of different stages. Our results might show an overview of what is happening in patients with precancerous lesions and cervical cancer, and may give an early clue as to whom to administer monoclonal checkpoint blocking therapies.

Peer review status:IN REVISION

06 May 2020Submitted to Clinical & Experimental Immunology
06 May 2020Assigned to Editor
06 May 2020Submission Checks Completed
11 May 2020Reviewer(s) Assigned
28 May 2020Review(s) Completed, Editorial Evaluation Pending
04 Jun 2020Editorial Decision: Revise Major