An Intratumoral B-Cell Immune Response Determines Favorable Prognosis for Early Stage Lung Cancer and Can Be Assessed by Different Immunoscores
Julian Sanz, Susana Hernandez, Florentino Hernando, Jose Luis G Larriba, Javier Puente, Milagros Ferrer, Beatriz Perez Villamil, Jose L Subiza. Hospital Clinico San Carlos, Madrid, Spain
Background: One third of patients with early stage NSCLC will relapse before 5 years after surgery. There is enough evidence that immune response against tumour is crucial and an efficient immuno-score is required to improve prognosis and therapy decisions. By unsupervised whole genome expression profiling we found and validate a 50-gene signature as the best predictor for disease free survival (DFS) in stage I/II NSCLC compared with TNM and other variables. The vast majority of the 50 genes were associated with a B cell humoral response. Our aim was to compare inmunoscores by morphology, immunophenotype or gene expression.
Design: 84 resected R0 stage I /II NSCLC without adjuvant therapy. Recurrence: 34.5%. TNM, clinicopathological variables, EGFR and Kras mutations, microarray expression and 50-gene signature, chronic inflammation on H-E, semiquantitatively by IHC for CD3, CD4, CD8, granzyme B, CD20, CD57, CD79 and CD19, Univariate and multivariate analysis for DFS were assessed.
Results: In our series, clinicopathological variables incluing TNM were not associated with DFS. K-ras mutations showed a tendency (p=0.07) and only immune scores showed significant association with DFS.
The best predictor/ immunoscore was the 50-gene signature (HR=3.44; p=0.001) that identified 1/3 of patients with good prognosis including both AC and SCC, stage I and II. Presence of CD20+ cells (>60 cells/mm3) in the center of the tumour was detected in 50% of cases associated with favorable prognosis (p=0.05). Morphologic evaluation of inflammation on H-E slides, T-cell and NK cells IHC markers, were not useful prognostic indicators. CD79 showed a tendency (p=0.08).
Conclusions: A B-cell immune response from B/plasma cells infiltrating the tumor is the best predictor of DFS for completely resected NSCLC. It can be more precisely assessed by expression profiling but also CD20 IHC could be a useful immunescore. Although immune mechanisms with cancer prognostic value have been related mainly to Tcells, some recent studies point to a key role for humoral adaptive immune response. Indeed, we can classify a subgroup of patients with very low risk of recurrence associated to a B-cell response, that may be candidates to avoid the toxicity of adjuvant therapy.
Tuesday, March 5, 2013 1:30 PM
Proffered Papers: Section D, Tuesday Afternoon