Understanding The Influence of Tumour Microenvironment Variability On Therapeutic Effectiveness

Abstract

Cancer immunotherapy has proven effective in treating malignant diseases, but only a small percentage of patients experience completeand durable responses to current treatments. This highlights the need for more effective immunotherapies, combination treatments, andpredictive biomarkers. The molecular properties of a tumor, intratumor heterogeneity, and the tumor immune microenvironment are key targetsfor precision cancer medicine. Humanized mice that support the engraftment of patient-derived tumors and recapitulate the human tumorimmune microenvironment of patients represent a promising preclinical model for addressing fundamental questions in precision immuno-oncology and cancer immunotherapy. The microenvironmental physiology of tumors is unique from normal tissues, characterized by oxygendepletion, glucose and energy deprivation, high lactate levels, and extracellular acidosis. Hypoxia and other hostile microenvironmental parameterscan confer resistance to irradiation, leading to treatment failure. Pretreatment assessment of critical microenvironmental parameters is neededto select patients who could benefit from special treatment approaches, such as hypoxia-targeting therapy. Acquired resistance to varioustherapeutic interventions is a hallmark of cancer, and the tumor microenvironment (TME) plays a crucial role in cancer progression, particularlytherapeutic resistance. Targeting the TME as an essential strategy to overcome cancer resistance and improve therapeutic outcomes throughprecise intervention is highly desired. Cell stem cells (CSCs) play a pivotal role in tumorigenesis, tumor progression, and metastasis. Theinflammatory microenvironment is an essential component of the tumor microenvironment, and understanding the key factors that exertimportant actions in the tumor process would be important to improve clinical outcomes.