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Poster Discussion session - Translational research 1

5226 - Pre-treatment CD4 senescent T cells accurately predicts lack of response to PD-L1/PD-1 immune checkpoint blockade in non small cell lung cancer, and correlates with risk of hyperprogression


20 Oct 2018


Poster Discussion session - Translational research 1


Translational Research

Tumour Site


Miren Zuazo


Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269


M. Zuazo1, H. Arasanz2, M. Gato-Cañas3, G. Fernández-Hinojal4, B. Hernández-Marín5, M. Martínez-Aguillo6, M. Ibáñez-Vea1, M.J. Lecumberri Biurrun4, Á. Fernández de Lascoiti4, R. Vera7, G. Kochan1, D. Escors1

Author affiliations

  • 1 Immunomodulation-oncology, Navarrabiomed, 31008 - Pamplona/ES
  • 2 Immunomodulation-oncology, Navarrabiomed / Fundación Miguel Servet, Pamplona/ES
  • 3 Inmunomodulación, Navarrabiomed / Fundación Miguel Servet, Pamplona/ES
  • 4 Medical Oncology, Complejo Hospitalario de Navarra, Pamplona/ES
  • 5 Medical Oncology, Complejo Hospitalario de Navarra, 66 - Pamplona/ES
  • 6 Medical Oncology, Complejo Hospitalario de Navarra, 55 - Pamplona/ES
  • 7 Medical Oncology, Complejo Hospitalario de Navarra, 31008 - Pamplona/ES


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Abstract 5226


PDL1-PD1 blockade therapies are demonstrating promising clinical outcomes in NSCLC (non-small cell lung carcinoma) patients. However, a significant proportion of patients are intrinsically resistant to these therapies. Moreover, instead of raising efficacious anti-tumor immunity, this therapy might accelerate disease carrying hyperprogression. Hence, stratification of patients into hyperprogressors, non-responders and potential responders is a critical issue in oncology.


Peripheral blood samples from 34 NSCLC patients treated with PD-L1/PD-1 immune checkpoint inhibitors were obtained previous to the initiation of the immunotherapy and before the administration of each cycle of treatment. Baseline CD4+ Tsen numbers and their dynamic changes during treatment were quantified by flow cytometry and correlated to responses and survival.


In our cohort study, patients with baseline Tsen values below 40% (negative profile) had an ORR of 0% and all experienced progression by week 9; in contrast to patients with Tsen values above 40% with ORR accounted to 38.9% and a 12-week PFS of 44%. Moreover, two main systemic T cell dynamic patterns were identified. Increase in Tsens after the first cycle of therapy was always associated to hyperprogression and intrinsic non-responders (pattern 1, Tsen “burst”), while decrease (pattern 2) significantly correlated with responders. Here, we demonstrate that a Tsen baseline value <40% associated to significant “Tsens bursts” thorough therapy objectively characterized hyperprogressive disease. ROC analysis demonstrated the robustness of Tsen quantification with clinical output (R = 0.84, P = 0.006), with a cut-off value of < 57.7% baseline Tsens to achieve 100% specificity with a 75% sensitivity for identification of non-responders prior to therapy.


This study uncovers the central role of CD4+ Tsen cells in anti-PD-L1/PD-1 immunotherapy efficacy, and provides a highly accurate predictive biomarker of responses to PD-L1/PD-1 blockade. Baseline CD4+ Tsen values unequivocally identify hyperprogressors and intrinsic non-responders before therapy administration.

Clinical trial identification

Legal entity responsible for the study

Navarrabiomed-Fundación Miguel Servet.


Asociación Española Contra el Cáncer; Instituto de Salud Carlos III, Spain; FECYT, Spain.

Editorial Acknowledgement


All authors have declared no conflicts of interest.

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