4643 - Combined immunoscore for prognostic stratification of early stage NSCLC patients

Background

Tumor 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.

Methods

Surgical 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.

Results

Preliminary 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.

Conclusions

The 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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Istituto Oncologico Veneto IRCCS.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.