Reduced number and impaired effector functions of TILs in tumors with PTEN deletion or loss-of-function mutations in PTEN. Cutaneous melanoma patients whose information was included in TCGA were stratified based on the PTEN CN (cutoff, ≤−0.4, which was chos... Reduced number and impaired effector functions of TILs in tumors with PTEN deletion or loss-of-function mutations in PTEN. Cutaneous melanoma patients whose information was included in TCGA were stratified based on the PTEN CN (cutoff, ≤−0.4, which was chosen in order to maximize the difference in the level of activity of the AKT pathway). A box-and-whisker plot was used to demonstrate the differences in expression levels of indicated genes or proteins between these two groups. A, comparison of the intensity of phosphorylated AKT and LCK in melanomas obtained from patients with different PTEN CNs according to RPPA. B, the mRNA expression levels for genes encoding IFNγ and granzyme B in tumor samples obtained from melanoma patients with different PTEN CNs. C, comparison of lymphocytic infiltration score (Lscore), as determined by pathological review, between groups of patients with different PTEN CNs. The P values of the comparisons were determined by unpaired t test. D, frequencies of genetic alterations in the β-catenin pathway and PTEN between T cell–inflamed and non-T cell–inflamed tumors. Metastatic melanomas from TCGA were first catalogued based on T-cell infiltration and subsequently based on activating mutations in β-catenin itself (CTNNB1) or loss-of-function (LOF) mutations in negative regulators of the β-catenin pathway (APC, APC2, AXIN1, and AXIN2), and PTEN deletion or PTEN mutations. Non-T cell–inflamed tumors have an increased frequency of PTEN alterations compared to the T cell–inflamed tumors (P < 0.01 by Fisher exact test). Weiyi Peng et al. Cancer Discov 2016;6:202-216 ©2016 by American Association for Cancer Research