Blood and lymphatic vessels contribute to the impact of the immune microenvironment on clinical outcome in non-small-cell lung cancer†

Abstract

Microvessels are an essential component of the cancer immune microenvironment. The clinical impact of the PD-1/PD-L1-based immune contexture may be implemented by the assessment of microvascular density to potentially identify patients with non-small-cell lung cancer who could benefit from immunotherapy and antiangiogenic treatment.

A Spatial Quantitative Systems Pharmacology Platform spQSP-IO for Simulations of Tumor–Immune Interactions and Effects of Checkpoint Inhibitor Immunotherapy

“…During initialization, entry points for T cell recruitment representing tumor vasculature are randomly created. The density of these entry points can be chosen depending on relative vascular density in different regions of a tumor; experimental data on tumor vasculature can be used to guide this process [63][64][65].…”

“…To illustrate this, we employed a version of the model with two volumes representing tumor invasive front and tumor core, respectively and varied the vascular density parameter in these two volumes. This parameter is chosen based on observations from experimental and clinical data indicating that there are differences in tumor vasculature and blood perfusion among these regions [63][64][65]. In the simulations, we tested four different scenarios, with vascular density increased by 10× in tumor core, on the stromal side of the invasive front, on the tumor side of the invasive front, and one negative control where vascular density is kept the same in all ABM regions.…”

Methods for studying pulmonary lymphatics

“…These techniques allow for experimental intervention in vitro. This approach has been used to study the role of lymphatics in asthma [22], COPD [23], transplantation [24] and cancer [25], as well as an avenue to develop therapeutics [26] that modulate lymphangiogenesis. Cells obtained via this method can be studied using various tissue-based techniques, including proliferation assays, chemotaxis evaluation, tube formation assays, protein expression assays, electric cell substrate impedance sensing and flow cytometry, among others.…”

Identification of prognostic genes in lung adenocarcinoma immune microenvironment

“…Malignant tumor cells, mesenchymal cells, inflammatory mediators, endothelial cells, stromal cells, immune cells, and normal epithelial cells are involved to constitute the microenvironment of tumor. [ 3 ] For the development of prognostic and predictive biomarkers, an in-depth study on the expression of related genes in tumor immune microenvironment is of much significance. To assess the stromal and immune cells in tumor samples for their infiltration, Yoshihara et al [ 4 ] designed an algorithm known as ESTIMATE to predict the number of stromal and immune cells in tumor samples based on the unique characteristics of the transcriptional profiles of cancer samples.…”

“…Recently, the focus of cancer-related research has been gradually turned to the tumor microenvironment based on cell biology and molecular mechanisms, which plays a major role in the progression of cancer including LUAD. Malignant tumor cells, mesenchymal cells, inflammatory mediators, endothelial cells, stromal cells, immune cells, and normal epithelial cells are involved to constitute the microenvironment of tumor [3] . For the development of prognostic and predictive biomarkers, an in-depth study on the expression of related genes in tumor immune microenvironment is of much significance.…”