Abstract

BackgroundTumor infiltrating lymphocytes (TILs) and PD-L1 expression have been previously associated with early stage NSCLC prognosis. Most data refer to intra-tumoral (IT) lymphocytes, while evidence on the prognostic role of the tumor immune microenvironment (TME) as a whole is lacking. Moreover, a combined immuno-score (IS) including more than two markers, is currently not available. We investigated the prognostic impact of PD-L1 expression and different immune cell infiltrates (CD3+CD4+, CD3+CD8+ T-lymphocytes and CD68+ macrophages) at peritumoral (PT) and IT level. MethodsSurgical specimens from chemo-naive stage II-III NSCLC patients radically resected between 2015 and 2017 were analyzed. Immunohistochemistry was carried out to evaluate PD-L1 expression (low <50%, high³50%), and to quantify IT, PT and total CD3+CD4+, CD3+CD8+ T-lymphocytes and CD68+ macrophages. The impact of single marker and of a combination of multiple significant markers on overall survival (OS) was investigated. ResultsPreliminary data of 79 patients are reported; eligible cases were 51(65%) adenocarcinoma and 28(35%) squamous cell carcinoma, 31(39%) stage II and 48(61%) stage III. Median follow-up was 2.5 years. Higher PD-L1 expression identified cases with worse prognosis (2.5 years OS 58% in high compared with 74% in low expressing tumors), even though without statistical significance. Shorter OS was observed in cases with higher PT CD3+CD8+(p=0.015), CD3+CD4+(p=0.047) and CD68+(p=0.047). These three parameters were put together into a combined IS (2/3 low: low, 2/3 high: high) which confirmed a prognostic stratification of evaluated patients (2.5 years OS 96% vs 63% respectively in low and high IS, p=0.004), also at multivariate analysis. The prognostic impact of combined IS within each pathologic stage was confirmed. IT T-lymphocytes and macrophages infiltrate did not show a negative prognostic impact; 2.5 years OS of 94% vs 67% (p=0,033) was observed in highe and lower PT-CD8+/IT-CD8+ ratio, respectively. ConclusionsThe amount of PT T-lymphocytes and macrophages might allow early-stage NSCLC patients prognostic stratification for adjuvant strategy plan, especially within a combined immuno-score including multiple TME actors. Legal entity responsible for the studyIstituto Oncologico Veneto IRCCS. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

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