Cancer Microenvironment and Cancer Vaccine

Abstract

The cancer microenvironment is constituted of non-transformed host stromal cells such as endothelial cells, fibroblasts, various immune cells, and a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it. The importance of the microenvironment and its potential in cancer therapy is just being established. Among modalities that target the microenvironment, cancer vaccine is a unique strategy which is aimed to elicit specific immunity against components in the microenvironment. Most, if not all, components can be targeted by the vaccines. The most extensively studied are the endothelial cells, fibroblasts and macrophages as well as ECM. Vaccines are in development for each of them. All the vaccines were proved to be effective at providing protective or therapeutic anti-tumor effects in the pre-clinical models. A few of them have been tested in the clinical trials. The mechanisms of the vaccines were mainly related to the cellular immune response such as CD8+ cytotoxic T cells, and in some instances CD4+ Th cells were involved as well. The present review also discussed the hurdles associated with the microenvironment-based vaccines such as the selection of suitable patients with appropriate biomarkers. With the rapid increase of our knowledge in the cancer microenvironment, the proof-of-concept of microenvironment-based cancer vaccines will surely expand our armamentarium against cancer.

T cells in tumor microenvironment

“…As it is expected, carcinogenesis is affected not only by the epithelial cells but also by the other types of cells such as inflammatory cells, fibroblasts, and immune cells such as dendritic cells and macrophages [1,7]. Angiogenesis, which is an essential phenomenon for the initiation of cancer and propagation as metastasis, provides the transportation of necessary molecules for the growth of cancer cells such as oxygen and nutrients between normal blood vessels and tumor cells by the formation of special vessel for cancer cells.…”

“…The development and propagation of cancer depend on not only cancer cells and cancer stem cells within tissue but also other necessary components, which can be named as cancer microenvironment that is regarded as cancer bed and involves many kinds of resident and non-resident constituents [1,2]. Cancer as a very complex disease includes both the transformed cells and non-transformed cells as host stromal cells that involve endothelial cells, fibroblasts, immune cells, and complex extracellular matrix [3].…”

“…Angiogenesis, which is an essential phenomenon for the initiation of cancer and propagation as metastasis, provides the transportation of necessary molecules for the growth of cancer cells such as oxygen and nutrients between normal blood vessels and tumor cells by the formation of special vessel for cancer cells. For this reason, the formation of angiogenesis depends on the existence of endothelial cells in the tumor microenvironment [1,8].…”

“…In this environment, they act as a regulatory component of tumor cells' specific phenomena such as metastasis, carcinogenesis, and therapy resistance and they can include mesenchymal cells, endothelial cells, and epithelial cells as a heterogeneous population [1,[9][10][11]. Those CAFs as prominent regulatory components are also regulated by cancer cells in terms of with some activator molecules [4].…”

“…In addition, extracellular matrix (ECM) can affect the fate of tumor. ECM establishes the direct contact with newly forming cancer cells and it can promote the conversion to malignant tumor and metastasis by majorly supporting the secretion of different cytokines [1,22] (Fig. 1).…”