This lecture will describe the formation, remodeling, maintenance, and function of the immune landscape of cancer. Specifically, the formation of the tumor-immune environment at the earliest stages of tumor development, its heterogeneity and constantly evolving phenotypes, the physiological processes that regulate innate and adaptive immune responses, and the role of adaptive evolution within the tumor will be discussed in the context of how they determine the duration and efficacy of anti-tumor immune responses. This presentation is organized in three topics. The first topic covers the formation of the tumor immune environment and is subdivided into three sections that will focus on (1) inflammation and cancer, (2) the immune response to cancer, and (3) the development of the tumor-immune environment. The second topic describes a cross sectional view of the tumor-immune landscape and is also subdivided into three sections that will focus on (1) the definition of the tumor-immune landscape, (2) the composition and complexity of the tumor-immune landscape, and (3) the clinical significance of the tumor-immune landscape. The final topic describes the evolution of the tumor-immune landscape and is subdivided into four sections that will focus on (1) the innate response to tumor formation, (2), the dynamic interactions between the tumor and the immune system, (3) the role of mutational neoantigens in the anti-tumor immune response, and (4) immunoediting, or the success or failure of anti-tumor immunity. An important conclusion from this lecture is that breaking the tumor immunosuppressive barrier(s) is an absolute condition that must be achieved if cancer immunotherapies are to be successful.

Learning Objectives:

1. Appreciate the steps and the mechanisms that lead to the formation of the immunosuppressive barrier
2. Recognize the heterogeneity of the tumor-immune landscape and the limitations of reducing that landscape to a few types or categories
3. Understand the opportunities and limitations for immunomodulation and immunotherapy across the diversity of cancers