189P - The parallel interrogation of tissue and peripheral blood immune features unveils a bidirectional crosstalk with clinical impact on resected NSCLC

Background

The cancer-immune interplay and its role on the evolution of NSCLC might be disclosed through the detection of local and systemic cues. Aim: To determine whether peripheral blood (PB) immune profiles may mirror clinically relevant tumor immune microenvironmental (TIME) features in resected NSCLC patients.

Methods

Tissue and PB samples were prospectively collected at surgery from 80 consecutive stage I-IIIA NSCLC cases. The immunohistochemical evaluation of TIME involved PD-L1 status and spatial distribution of CD3+, CD4+, CD8+, PD1+ Tumor Infiltrating Lymphocytes (TILs), defined as immune efficient (IEff) when in contact with cancer cells or immune excluded (IEx) when trapped in fibrosis. TILs clustering was also considered. PB CD3+, CD4+ and CD8+ lymphocytes, NKs, and Tregs together with the expression of PD1, Granzyme B (GnZ) and Perforin (Perf) were assessed by flowcytometry. TIME-PB relationships and their clinico-pathological correlates were statistically examined.

Results

Compared to stage II and III, TIME from stage I revealed increased CD3, CD8 and CD4 clusters (P = 0.03) coupled with higher PB CD8+ and CD4+ lymphocytes (P = 0.02). Females displayed greater IEff and clustered CD3 and CD8 TILs and higher PB CD4, while males exhibited more distally located TILs and predominant PB GnZ+ CD8+ (P < 0.05). Blood from PD-L1^pos NSCLC showed a significant immune switch favoring CD8 (P = 0.007), while PD-L1^neg cases presented higher PB CD4 (P = 0.02) with predominant Tregs (P = 0.05) phenotype. Tissue CD4-to-CD8 ratio and CD8 TILs density were directly correlated with blood CD4/CD8 (P = 0.002) and CD8 number (P = 0.05), whereas an opposite trend between IEff CD8 TILs and PB Tregs was detected. Tissue PD1-to-CD8 ratio was inversely related to the fraction of CD8+PD1+ in PB. Intriguingly, early recurrent NSCLC patients were characterized by TIME carrying 1.5-fold higher PD1-to-CD8 ratio and lower CD8+PD1+ cells in PB, supporting the double edge sword of PD1 receptor.

Conclusions

Blood shares relevant immune features with TIME, providing an exploitable noninvasive tool to intercept the cancer immunity cycle and its targetable pathways.

Legal entity responsible for the study

University Hospital of Parma.

Funding

AIRC – The Italian Foundation for Cancer Research.

Disclosure

All authors have declared no conflicts of interest.