Modulating inflammation for cancer therapy

Abstract

A link between chronic inflammation and development of tumors is well established. Moreover, it has become evident that tumorigenesis is not a cell autonomous disease, and an inflammatory microenvironment is a prerequisite of basically all tumors, including those that emerge in the absence of overt inflammation. This knowledge has led to the development of anti-inflammatory concepts to treat and prevent cancer. In contrast, immunotherapies, in particular checkpoint inhibitors, representing the most significant progress in the therapy of several malignancies depend on the presence of a pro-inflammatory "hot" environment. Here, we discuss pro- and anti-inflammatory concepts for the treatment of cancer.

Figure 1.

Time course from first documented cancer cases to modern therapy. Ab, antibody; ABL, Abelson murine leukemia viral oncogene homologue 1; AML, acute myeloid leukemia; CAR, chimeric antigen receptor; CML, chronic myeloid leukemia; CTCL, cutaneous T cell lymphoma; RA, rheumatoid arthritis; T-VEC, talimogene laherparepvec; VEGF, vascular endothelial growth factor.

Figure 2.

Tumor immune statuses. Infiltration-excluded tumors (left) accumulate cytotoxic T lymphocytes (CTLs) around their margins, where they interact with Ly6c^loF4/80^hi TAMs or are impeded by cancer-associated fibroblasts (CAFs). Infiltration-inflamed tumors (right) show activated PD1⁺ CTLs in their core that express IFNγ and granzyme B (GrzB). They may form tertiary lymphoid structures and are generally associated with good prognosis and response to ICB. Therefore, therapies aim to promote this state. DC, dendritic cell; IDO, indoleamine (2,3)-dioxygenase; MSI, microsatellite instability.