Abstract 1650: Prognostic importance of both stage of the disease and immune infiltrate in the outcome of NSCLC patients
Authors: Dieu-Nosjean Marie-Caroline , GOC Jeremy , GERMAIN Claire , KNOCKAERT Samantha , Alifano Marco , LUPO Audrey , Damotte Diane , Validire Pierre , HAMMOND Scott SA , Fridman Wolf-Herman , Sautes-Fridman Catherine 
Published: May 2015

Abstract
The majority of prognostic studies has highlighted a positive impact of intratumoral T cells on the survival of patients affected by solid tumors. The high reproducibility of these data strongly support the idea that one should take into account immune criteria for the prognostic staging of neoplastic lesions. Several studies have indeed reported a favorable clinical outcome for lung cancers patients whose neoplastic lesions contain a high density of CD8+ T cells. Moreover, we recently showed that mature dendritic cells (DC) were selectively detected in tertiary lymphoid structures (TLS) in lung cancer. We showed that TLS exhibit strong structural analogies with canonical secondary lymphoid organs with clusters of mature DC and T cells surrounded by B cell follicles. Lung cancer-associated TLS also present features of an ongoing immune reaction site. Interestingly, we reported that a high density of mature DC is correlated with the long-term survival of patients affected by early-stage, advanced and metastatic lung cancer. The combination of mature DC and CD8+ T cells allows the identification of patients with the highest risk of death. Thus, the survival of lung cancer patients appears to be positively influenced by the abundance of both cell types. This raises the question of evaluating the clinical impact of these tumor-infiltrating immune cells in combination with pathological parameters in lung cancer patients.
A total of 372 patients operated for a lung cancer were enrolled in a retrospective study. Using immunohistochemistry, we demonstrated that combination of the density of mature DC and CD8+ T cells, with the pT stage better predicts the overall survival of lung cancer patients than the gold standard pT stage alone. The DC/CD8 score with the N stage allow a better discrimination of patients with high- versus low-risk of death, especially in the group of patients with lymph node invasion. We also demonstrated that the combination of DC/CD8 and emboli parameters allow a better stratification of lung cancer patients for survival. Finally, the DC/CD8 score enhances the prognostic value of the TNM stage. Combining DC/CD8 score with the pTNM stage yields a more refined view of the prognosis of lung cancer patients.
In conclusion, DC/CD8 score becomes prognosticator of survival for patients with first signs of metastasis (lymph node involvement, vascular and/or lymphatic tumor invasion). This study contributes to a better understanding of beneficial elements of immune responses to tumors. Combining DC/CD8 score with the stage of the tumor could guide better treatment choices.
Citation Format: Marie-Caroline Dieu-Nosjean, Jeremy GOC, Claire GERMAIN, Samantha KNOCKAERT, Marco Alifano, Audrey LUPO, Diane Damotte, Pierre Validire, Scott SA HAMMOND, Wolf-Herman Fridman, Catherine Sautes-Fridman. Prognostic importance of both stage of the disease and immune infiltrate in the outcome of NSCLC patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1650. doi:10.1158/1538-7445.AM2014-1650