Abstract 1061P
Background
Parallel monitoring of radiomic and blood/tissue immunophenotypic cues may intercept the critical events implicated in Immune Checkpoint Inhibitors (ICIs) efficacy. Thus, we explored radio-immune features and their evolution to provide suitable predictors of ICI response in advanced NSCLC patients.
Methods
On 58 ICI treated NSCLC cases, we prospectively evaluated: Tumor Immune Microenvironment (TIME) by PD-L1 expression and incidence and spatial distribution of infiltrating lymphocytes (TILs); peripheral blood (PB) at T0 and first disease assessment (T1) for the quantification of effector (NK, CD8, PD1, Granzyme B [GnzB], Perforin [Perf], Ki67) and suppressor (CD4+CD25+FOXP3+ Tregs) phenotypes (flowcytometry), soluble PD-L1 (sPD-L1) and Lung Immune Prognostic Index (LIPI); CT derived Radiomic Features (RFs, n: 851) at T0 and T1. Changes in PB parameters were expressed as Δ% = ([T1 - T0]/T0)*100, while ΔRFs as (T1-T0)/T0. Primary endpoint was tumor response (RECIST v.1.1): CR/PR or SD ≥ 6 months defined clinical benefit (CB), while SD < 6 months or PD non-responders (NR).
Results
Baseline immune profile of CB patients comprised: -TIME enriched of CD3+, CD8+ and PD1+ and poor of immune excluded (IE) TILs (Mann-Whitney, p<0.01 vs NR); -PB bearing prominent effector cells, low sPD-L1 and good LIPI, enclosing a highly prognostic model (Fisher, p<0.005). Among PB-TIME associations, PB Tregs correlated directly with IE and inversely with intratumor-CD8+ TILs (p<0.05). Mean Δ% NK, CD8+Ki67+ and CD8+GnzB/Perf+ were, respectively, -20%, -0.4% and -41% in NR and +22%, +170% and +65% in CB, which also displayed a greater boost of counterregulatory Tregs (p<0.05). Out of 657 ΔRFs resulting from pre-processing and Z-score standardization, 11 were differentially regulated in CB vs NR (Mann Whitney, p<0.05). Distinct ΔRFs principal components, encompassing wavelet-HLL_firstorder_Maximum and -HLL_firstorder_Skewness, showed, respectively, direct and inverse correlation with Δ% CD8+Ki67+ lymphocytes.
Conclusions
Static and dynamic radio-immune signatures may discern ICI outcome in advanced NSCLC, ultimately enabling tailored therapeutic approaches.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University Hospital of Parma.
Funding
AIRC.
Disclosure
All authors have declared no conflicts of interest.