Lymphocytic Host Response – An Adaptive T Cell Response at Tumor Interface & Relationship with HPV
S Maleki, F Macian, N Schlecht, J Diaz, J Moss, M Brandwein-Gensler, M Prystowsky. Montefiore, Bronx, NY; Einstein, Bronx, NY
Background: Lymphocytic host response (LHR) in the Risk Model is quantified as density of inflammatory cells at the tumor interface. It is classified as strong (LHR1), moderate (LHR2) or limited (LHR3) and associates with the risk of disease progression. HPV16 is associated with a subset of HNSCC, and HPV+HNSCC may respond better to chemoradiotherapy with longer survival, although the mechanism is still unclear. We test two hypotheses: 1) Strong LHR corresponds to an adaptive cytotoxic T cell response, 2) transcriptionally active HPV+ HNSCC are associated with strong LHR.
Design: We compared oral resections with strong (15), intermediate (19) and weak (4) LHR. CD3, CD4, CD8, & CD20 cells were quantified at 40X with a grid; counting 10 densest fields at tumor interface and within tumors. Mean counts/tumor were analyzed by the 2-sided T-test. Frozen SCC from a larger set of 63 SCC were tested for active HPV16 E6/E7 by RT-PCR and corresponding LHR was assessed.
Results: Tumors with strong LHR 1 have significantly increased CD3 & CD8 counts at the tumor interface compared to intermediate LHR 2 (p<0.001, p=0.009, respectively). There were no differences with CD20 (interface & intratumor) or CD4 (interface) in LHR1 & LHR2 SCC. CD3/CD4/CD8 cell counts within tumors, across LHR groups were not significantly different, but trends were suggested. Figure 1 shows mean cell counts (CD3/CD8) at the tumor interface and within tumors, for strong, intermediate, and weak LHR.
A trend was seen with active HPV and LHR1 (score test for trend of odds p = 0.081). Tumors with transcriptionally active HPV infection were likely to have strong LHR1 when adjusted for tumor site and stage (Mantel Haenszel odds ratio 1.65, 95% CI 0.5, 5.9), albeit not signficantly.
Conclusions: Immune response at the tumor interface correlates with an adaptive T cell response, and strong LHR correlates with increased cytotoxic T cells at the interface. The association between active HPV16 and LHR1 supports increased immune surveillance as one mechanism of enhanced survival of patients with HPV+HNSCC. Our next goal is to quantify activated vs. post-activated CD8 and CD4 cells by immunoflourescence.
Category: Head & Neck
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 161, Tuesday Afternoon