Improving immune–vascular crosstalk for cancer immunotherapy

Abstract

The vasculature of tumours is highly abnormal and dysfunctional. Consequently, immune effector cells have an impaired ability to penetrate into solid tumours and often exhibit compromised functions. Normalization of the tumour vasculature can enhance tissue perfusion and improve immune effector cell infiltration, leading to immunotherapy potentiation. However, recent studies, have demonstrated that stimulation of immune cell functions can also help to normalize tumour vessels. In this Opinion article, we propose that the reciprocal regulation between tumour vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumour immune microenvironment to induce durable antitumour immunity. A deeper understanding of these pathways could pave the way for identifying new biomarkers and developing more effective combination treatment strategies for patients with cancer.

Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak

“…ARDS induced by cytokine storm is reported to be the main reason for death of SARS-COV-2-infected patients (18). It is possible that in this setting, immunotherapy induces the release of a large amount of cytokines, which can be toxic to normal cells, including lung epithelial cells (19)(20)(21), and therefore lead to a more severe illness. However, in this study the number of patients with immunotherapy was too small; further research with a large case population needs to be conducted in the future.…”

Redefining mesothelioma types as a continuum uncovers the immune and vascular systems as key players in the diagnosis and prognosis of this disease

“…MPM being refractory to chemotherapy and radiotherapy, the major translational interest is the identification of novel and promising therapeutic options, especially for the sarcomatoid and biphasic types. Several recent reviews have nicely summarized how the tumour-associated blood and lymphatic vasculature play an important role in avoiding tumour destruction, as well as the therapeutic opportunities to overcome this immune blockage (12)(13)(14)(15). Recent data from ongoing clinical trials presented in the iMig 2018 conference hold in Ottawa (Canada) pointed that, while immunotherapy remains promising in the treatment of a subset of mesothelioma patients, there is an urgent need to identify novel and better predictive markers of response (16).…”

“…S5e-g, but including only the 130 epithelioid samples. 13 Kaplan-Meier survival curve of the four regions highlighted in (a). c) Median (solid line) and 95% quantiles (filled shapes) of the expression level, measured in normalized read counts, of angiogenesis-related genes significantly associated with PC1: VEGFR1, VEGFR2, VEGFR3, VEGFC, and PDGFRB.…”

Detecting Early Response to Immune Checkpoint Blockade by Multimodal Molecular Imaging

“…It is also well known that tumor cells create a challenging environment for the immune system characterized by hypoxia, low pH, high interstitial fluid pressure, and immune-inhibitory metabolites such as lactic acid 13,14 . The impaired perfusion capacity of tumor blood vessels by abnormal tumor vasculature create a highly hypoxic microenvironment, frequently resulting in immune suppression 15 . Recent studies have demonstrated that tumor hypoxia is negatively associated with the efficacy of immunotherapy and that the stimulation of immune cell functions with PD-1 and CTLA-4 blockade can also help to normalize tumor vessels 16,17 .…”