Survival in Lung Adenocarcinoma and Mesothelioma Is Influenced by Ig-Like Transcript 3 Expressing Macrophages
NT Beaubier, CC Chang, S Alexander, N Suciu-Foca, AC Borczuk. Columbia University Medical Center, New York, NY
Background: Ig-like transcript 3 (ILT3) is a membrane bound receptor on antigen presenting cells (APC) that can sometimes be detected in soluble form. ILT3 induces CD8+ T suppressor cells, which in turn may be responsible for an ineffective immune response to neoplastic cells. Published reports have linked ILT3 expression to a diminished immune response to melanoma and gastrointestinal tract tumors. However, the relationship of ILT3 to survival in lung adenocarcinoma (AdCa) and malignant mesothelioma (MM) has not previously been studied.
Design: Tissue microarrays of clinically annotated lung AdCa (n = 167) and MM (n = 68) were immunostained with antibody to ILT3 and graded from 0 to 3 in the tumor cells, non-tumor stromal cells, and cells with dendritic morphology (dendritic pattern). Association with survival was calculated using Cox regression analysis and Kaplan-Meier curves with log rank statistic (SPSS version 16.0). Correlation with lymph node metastasis in lung tumors was also performed.
Results: Kaplan-Meier survival analysis showed that in lung AdCa the cases with the ILT3 positive dendritic pattern had a median survival of 1903 days while the cases without an ILT3 dendritic pattern had a significantly longer (p = 0.005) survival of 3200 days. In MM the survival time was 402 days for dendritic pattern and 1458 days in the absence of a dendritic pattern (p = 0.003). In addition, in lung AdCa there was a correlation between the dendritic pattern and lymph node metastases (Pearson chi-square = 5.5, p < 0.02). ILT3 tumor cell immunostaining was weak to absent overall and not correlated with survival. Non-tumor stromal staining was associated with survival in lung AdCa (HR 1.45 CI 1.01-2.06, p = 0.04), but not in MM. ILT3 immunostaining in alveolar macrophages was not associated with survival in lung AdCa. The dendritic pattern of immunostaining was associated with overall survival in lung AdCa (HR 1.24 CI 1.06-1.45, p = 0.007), and the association was significant in the subgroups of stage I&II tumors (n = 148), and stage I alone (n = 121). In MM the association between dendritic pattern and survival was also significant (HR 1.35 CI 1.08-1.69, p = 0.009).
Conclusions: These data show that the dendritic pattern of ILT3 expression by IHC is inversely correlated with survival in lung AdCa and MM. Since ILT3 is known to induce T suppressor cells, this result could be explained by the immune system becoming anergic to the tumor because of high ILT3 expression.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 227, Monday Morning