Tumor Immune Microenvironment in Cancer Progression and Cancer Therapy

Saraswoti Khadge, John Graham Sharp, Timothy R. McGuire, Geoffrey M. Thiele, James E. Talmadge

Rodent and clinical studies have documented that myeloid cell infiltration of tumors is associated with neutrophilia, lymphocytopenia and poor patient outcomes. This contrasts with lymphocyte infiltration of tumors, which is associated with improved outcomes. Lifestyle parameters such as high fat diet s and omega (ω)-6 polyunsaturated fatty acids (PUFA) intake may influence these inflammatory parameters including extramedullary myelopoiesis that can contribute to a metastatic "niche". While, tumor secretion of growth factors (GFs) and chemokines regulate tumor-immune-cell crosstalk, in this chapter, we also emphasize how lifestyle choices, including, obesity, high-fat and high ω-6 PUFA dietary content, contribute to inflammation and myeloid cell infiltration of tumors. A relationship between obesity and high-fat diets (notably the saturated fats in Western diets) and tumor incidence, metastasis, and poor outcomes is generally accepted. However, the mechanisms of dietary promotion of inflammatory microenvironments and targeted drugs to inhibit the clinical sequel remain an unmet challenge. One approach, modification of dietary intake may have a preventative or therapeutic approach to regulate tumor-associated inflammation and remains an attractive, but little studied intervention.