Rituximab treatment circumvents the prognostic impact of tumor infiltrating T-cells in follicular lymphoma patients

Publication date: Available online 13 April 2017
Source:Human Pathology
Author(s): Luc Xerri, Sarah Huet, Jeffrey M. Venstrom, Edith Szafer-Glusman, Bettina Fabiani, Danielle Canioni, Catherine Chassagne-Clément, Peggy Dartigues-Cuilléres, Fréderic Charlotte, Camille Laurent, Benedicte Gelas-Dore, Christopher R. Bolen, Elizabeth Punnoose, Reda Bouabdallah, Pauline Brice, Franck Morschhauser, Guillaume Cartron, Daniel Olive, Gilles Salles
Previous immunohistochemical (IHC) studies showed controversial data about the prognostic value of tumor infiltrating lymphocytes (TIL) in follicular lymphoma (FL). In order to clarify this issue, a large series of FL samples from rituximab-treated patients enrolled in the randomized PRIMA trial were examined. IHC was quantified using automated image analysis in 417, 287, 418, 406, 379, and 369 patients for CD3, CD4, CD8, PD1, ICOS, and FOXP3; respectively. RNAseq analysis was used to quantify TIL–related mRNA transcripts from 148 patients. When each IHC marker was used as a continuous variable in the whole cohort, high CD3 counts were associated with better progression free survival (PFS) (P=.025). When an optimal IHC cut-point was applied to the whole patient population, high CD3 counts and high PD1 counts were associated with better PFS (P=.011 and P=.044, respectively), whereas none of the other TIL markers had any significant correlation with outcome. When a stringent analysis was performed by dividing the whole cohort into a training set and a validation set, none of the TIL markers showed a prognostic significance in both groups. RNAseq analysis showed a significant correlation between high levels of CD3 and CD8 transcripts and better PFS (P=.001 and P=.037, respectively). No prognostic correlation was found as to the level of other immune gene transcripts. These results suggest that the IHC prognostic value of TILs is circumvented by rituximab treatment, although there is a trend for high numbers of CD3+ TILs to correlate with better PFS.



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