FIGURE 7.

mIF better predicts patient response—HNSCC. (A) Immune cell infiltrate densities at the tumor invasive margin are insufficient to predict favorable overall survival (OS) for oral squamous cell cancer patients. CD8+, FoxP3+, and PD-L1+ cell densities on both the tumor and stromal sides of the invasive margin were examined. Although higher densities CD8+ T cell showed some prognostic value, sufficient classification was lacking (Feng et al., 2017). (B) A positive correlation between an increased number of Tregs (FoxP3+) and CD8+ T cell infiltrates was observed; authors postulated that Tregs might not be close enough to the CD8+ T cells to suppress their effector function. In response, they developed a “Suppression Index.” This index reflected the number of FoxP3+ and PD-L1+ cells within a 3 “lymphocyte wide” or a 30 μm distance around CD8+ T cells. Using this index, patients were ranked for number of PD-L1+ and FoxP3+ cells within 30 μm distance around CD8+ T cells. Patients who were ranked in the top 50% for both PD-L1+ and FoxP3+ cells had a high suppression index with a low overall survival while those that did not rank in the top 50% for either PD-L1+ and FoxP3+ cells had a low suppression index and a high overall survival rate (Feng et al., 2017). (C) Analysis of the entire cohort demonstrates that by combining the suppressive index of both the stromal and tumor side of the invasive margin provides a cumulative suppressive index scoring system that better stratifies patients than conventional IHC. Multiplex IF plus spatial analysis of the proximity of FoxP3+ and PD-L1+ to CD8+ cells lead to a highly significant stepwise reduction of overall survival based on an increasing cumulative suppressive index and the development of a highly indicative prognostic marker superior to the prognostic index of the single markers (Feng et al., 2017). Publication copyright for Feng et al., 2017 is governed by a CC BY 4.0 License.