Integrating the Tumor Microenvironment into Cancer Therapy

Abstract

Tumor progression is mediated by reciprocal interaction between tumor cells and their surrounding tumor microenvironment (TME), which among other factors encompasses the extracellular milieu, immune cells, fibroblasts, and the vascular system. However, the complexity of cancer goes beyond the local interaction of tumor cells with their microenvironment. We are on the path to understanding cancer from a systemic viewpoint where the host macroenvironment also plays a crucial role in determining tumor progression. Indeed, growing evidence is emerging on the impact of the gut microbiota, metabolism, biomechanics, and the neuroimmunological axis on cancer. Thus, external factors capable of influencing the entire body system, such as emotional stress, surgery, or psychosocial factors, must be taken into consideration for enhanced management and treatment of cancer patients. In this article, we review prognostic and predictive biomarkers, as well as their potential evaluation and quantitative analysis. Our overarching aim is to open up new fields of study and intervention possibilities, within the framework of an integral vision of cancer as a functional tissue with the capacity to respond to different non-cytotoxic factors, hormonal, immunological, and mechanical forces, and others inducing stroma and tumor reprogramming.

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

“…It has been shown that the reciprocal interaction between the ECM and tumor and non-tumor cells such as myofibroblasts determines recruitment, activation, and reprogramming of stromal, inflammatory, and immune cells ( Sanegre et al, 2020 ). Despite the great similarity of reticulin scaffolding at the ITF of uADC and uLMS, we observed a differential immune infiltrate pattern, as informed by CD20, CD3, and CD8 markers.…”

Metabolic Classification and Intervention Opportunities for Tumor Energy Dysfunction

“…Recent studies based on nuclear transfection experiments [ 173 ], epigenetic changes, and metabolism deviations (e.g., pathways, Warburg effect, pH, and oxygenation) support the idea that alterations in cellular bioenergetic mechanisms trigger biophysicochemical tissue changes that we identify as cancer. Beyond the tumor cell itself and its aberrations, the tumor microenvironment regulates nutrition, metabolism, and oncometabolic interaction with the host immune response [ 174 ], and factors, such as nutrition, stress, and microbiota [ 175 ], are all involved in global energy function. Metabolic heterogeneity plays a role in genetic heterogeneity [ 176 ], metastatic capacity of tumor cells [ 4 ], stem cells, and determining metastasis organotropism [ 177 ].…”

Prognostic value of tumor immune cell infiltration patterns in colon adenocarcinoma based on systematic bioinformatics analysis

“…The tumor microenvironment (TME) is a vastly complicated cellular network composed of tumor cells, stromal cells, soluble factors, signal molecules, and extracellular matrix components [ 4 ]. Recent studies have revealed that the interactions between cancer cells and their surrounding TME could affect recruitment and activation of immune cells, tumor angiogenesis, and extracellular matrix remodeling, which determine tumor progression [ 5 , 6 ]. As an important part of TME, infiltrating immune cells, such as macrophages and lymphocytes, are considered to be highly relevant to tumor prognosis and influence the expression of immune-related genes in CRC [ 7 ].…”