Description: The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumor, nodes, metastasis (TNM) classification system based on tumor features is used for prognosis estimation and treatment recommendations in most cancers. However, the clinical outcome can vary significantly among patients within the same tumor stage and TNM classification does not predict response to therapy. Therefore, many efforts have been focused on the identification of new markers. Multiple tumor cell-based approaches have been proposed but very few have been translated into the clinic. The recent demonstration of the essential role of the immune system in tumor progression has allowed great advances in the understanding of this complex disease and in the design of novel therapies. The analysis of the immune infiltrate by imaging techniques in large patient cohorts highlighted the prognostic impact of the in situ immune cell infiltrate in tumors. Moreover, the characterization of the immune infiltrates (e.g. type, density, distribution within the tumor, phenotype, activation status) in patients treated with checkpoint-blockade strategies could provide information to predict the disease outcome. In colorectal cancer, we have developed a prognostic score (‘Immunoscore’) that takes into account the distribution of the density of both CD3 + lymphocytes and CD8 + cytotoxic T cells in the tumor core and the invasive margin that could outperform TNM staging. Currently, an international retrospective study is under way to validate the Immunoscore prognostic performance in patients with colon cancer. The use of Immunoscore in clinical practice could improve the patients’ prognostic assessment and therapeutic management.

Description: Purpose: Clear cell renal cell carcinoma (ccRCC) has shown durable responses to checkpoint blockade therapies. However, important gaps persist in the understanding of its immune microenvironment. This study aims to investigate the expression and prognostic significance of immune checkpoints in primary and metastatic ccRCC, in relation with mature dendritic cells (DC) and T-cell densities. Experimental Design: We investigated the infiltration and the localization of CD8 + T cells and mature DC, and the expression of immune checkpoints (PD-1, LAG-3, PD-L1, and PD-L2) in relation with prognosis, in 135 primary ccRCC tumors and 51 ccRCC lung metastases. RNA expression data for 496 primary ccRCC samples were used as confirmatory cohort. Results: We identify two groups of tumors with extensive CD8 + T-cell infiltrates. One group, characterized by high expression of immune checkpoints in the absence of fully functional mature DC, is associated with increased risk of disease progression. The second group, characterized by low expression of immune checkpoints and localization of mature DC in peritumoral immune aggregates (tertiary lymphoid structures), is associated with good prognosis. Conclusions: The expression of the immune checkpoints and the localization of DC in the tumor microenvironment modulate the clinical impact of CD8 + T cells in ccRCC. Clin Cancer Res; 21(13); 3031–40. ©2015 AACR .

Description: The Raman selection rules of the (Zn-Se, Be-Se)-mixed phonon-polariton ( P P ) created by “alloying” in the three-mode [1 × (Zn-Se), 2 × (Be-Se)] Zn 1−x Be x Se system, whose dramatic S-like dispersion (∼200 cm −1 ) covers the large frequency gap between the Zn-Se and Be-Se spectral ranges, are studied in its wave vector ( q ) dependence by near-forward Raman scattering. Both the “collapse” regime away from the Γ point (q = 0) and the “reinforcement” regime near Γ are addressed, using appropriate laser lines and Be contents. We find that in both regimes the considered P P , in fact a transverse mode with the mixed mechanical-electrical character, obeys the same nominal Raman selection rules as its purely mechanical variant observed in the standard backscattering geometry. The discussion is supported by contour modeling of the multi- P P Raman lineshapes in their q -dependence within the linear dielectric approach.