Classifying Cancers Based on T-cell Infiltration and PD-L1

Abstract

Cancer immunotherapy may become a major treatment backbone in many cancers over the next decade. There are numerous immune cell types found in cancers and many components of an immune reaction to cancer. Thus, the tumor has many strategies to evade an immune response. It has been proposed that four different types of tumor microenvironment exist based on the presence or absence of tumor-infiltrating lymphocytes and programmed death-ligand 1 (PD-L1) expression. We review this stratification and the latest in a series of results that shed light on new approaches for rationally designing ideal combination cancer therapies based on tumor immunology.

Figure 1. Types of tumor microenvironment to tailoring cancer immunotherapeutic modules

Cancers have been categorized into 4 different tumor microenvironments based on the presence of TILs and PD-L1 expression (15,16). They are type I (adaptive immune resistance), type II (immunological ignorance), type III (intrinsic induction), and type IV (tolerance). This proposed framework of stratifying tumors is simplistic but allows a platform to discuss the immunotherapeutic strategies best suited to targeting the four different tumor microenvironments. (Abbreviations: APC, antigen presenting cell; MDSC, myeloid derived suppressor cell; M2, M2 macrophage; PD-L1, programmed cell death 1 ligand 1; TCR, T cell receptor; T_H1, T helper 1; TIL, tumor-infiltrating lymphocyte)