Figure 1:

Tumor Immune Microenvironment (TIME) classification. Four different molecular groups according to B7–H1 (PD-L1) expression (y-axis) and the presence of TILs (x-axis) in tumor biopsies: (1) B7–H1-negative tumors without TILs, considered immunologically ignorant because immune cells do not accumulate at the tumor site; (2) PD-L1-positive tumors with TILs, considered a paradigm of adaptive resistance of tumors mediated by the PD-1 pathway, (3) PD-L1-negative tumors with TILs, characterized by tolerance because TILs are present, but do not produce IFN-γ to induce PD-L1 expression in the tumor microenvironment, and (4) PD-L1-positive tumors without TILs, which result intrinsic induction of PD-L1 expression in tumor cells through a variety of oncogenic pathways. Abbreviations: PD-1, programmed death-1; B7–H1, B7-homolog 1; TCR, T cell receptor; TIL, tumor infiltrating lymphocyte.