Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer

Sandra Salvi, Vincenzo Fontana, Simona Boccardo, Domenico Franco Merlo, Edoardo Margallo, Stefania Laurent, Anna Morabito, Erika Rijavec, Maria Giovanna Dal Bello, Marco Mora, Giovanni Battista Ratto, Francesco Grossi, Mauro Truini, Maria Pia Pistillo

Research output: Contribution to journalArticlepeer-review


The role of CTLA-4 in negative regulation of T-cell mediated immune response is particularly well established. Much less is known about its expression and function in tumour cells, and to our knowledge, no data are available on its possible impact on prognosis of NSCLC patients. We investigated CTLA-4 expression and prognostic role in 81 patients with radically resected stage I-III NSCLC. The analysis was performed by tissue microarray immunohistochemistry, and the median H-score of 20 was used as a threshold to deWne CTLA-4 overexpressing tumours. Correlation with standard prognostic factors was performed by using absolute and relative fold change indexes. Hazard ratios (HR) and corresponding 95% conWdence limits (95% CL) were computed through the Cox model. A higher frequency of CTLA-4 overexpression (>20) was found in non-squamous than in squamous NSCLC (52.8 vs. 35.7%) and in Ki67 ≤ 15 expressing tumours, as compared to those with Ki67 > 15 (51.5 vs. 38.7%). A reduced death rate was found in CTLA-4 overexpressing tumours (HR = 0.60, 95% CL = 0.28/1.23), and a further decrease was observed when considering tumours with CTLA-4 > 20 and Ki67 ≤ 15, in comparison with tumours with CTLA-4 ≤ 20 and Ki67 > 15 (HR = 0.41; 95% CL = 0.15/1.13). Our observational and exploratory study provides a Wrst and promising indication for an independent prognostic eVect of CTLA-4 overexpression in radically resected NSCLC. We presume that this eVect relies on modulation of the interaction of microscopic disease with CTLA-4-ligands expressing cells leading to NSCLC cell death.

Original languageEnglish
Pages (from-to)1463-1472
Number of pages10
JournalCancer Immunology, Immunotherapy
Issue number9
Publication statusPublished - Sep 2012


  • CTLA-4
  • Immunohistochemistry
  • Non-small cell lung cancer
  • Overall survival
  • Prognostic factor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy


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