Figure 4.
Colocalization of cells in the tumor microenvironment is associated with response to ICB
(A) Schematic representation of a tumor in which TILs are highly segregated away from tumor cells, yielding a low MH index (upper), and a tumor in which TILs are highly colocalized with tumor cells, yielding a high MH index (lower).
(B) Example images from a tumor with high colocalization of CD3+Foxp3- T cells and CD3+Foxp3+ Tregs.
(C) Boxplot illustrating significantly higher MH index scores for colocalization of T cells with Tregs (T_Treg) in patients who achieved a pCR. The data are depicted as individual dots for each sample, along with the median, first, and third quartile (n = 54 patients). Statistical analysis was performed using the likelihood-ratio test. ∗∗p < 0.05 (BH corrected).
(D) Example images from a tumor with high colocalization of CD3+PD-1+ T cells and PD-L1+ cells.
(E) Boxplot illustrating significantly higher MH index scores for colocalization of PD-1+ T cells with any PD-L1+ cell (PD1T_PDL1) in patients who achieved a pCR. The data are depicted as individual dots for each sample, along with the median, first, and third quartile (n = 54 patients). Statistical analysis was performed using the likelihood-ratio test. ∗∗p < 0.05 (BH corrected).
(F) Association dot matrix showing the level and direction of association between each MH index (columns) and pCR in the population/model as labeled (rows). Only those biomarkers that were significant (p < 0.05; after Benjamini-Hochberg multiple testing correction) in at least one cohort are shown. See Figure 3 legend for number of patients in each cohort (multi-IF platform). Color of dot indicates direction of association (red, higher in pCR; blue, higher in non-pCR). Size of dot is proportional to significance (larger dots → smaller p values). Background square color indicates: BH FDR p < 0.05 (white), nominal p < 0.05 (light gray), not significant (dark gray).