Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors

Motz, Gregory T.; Santoro, Stephen P.; Wang, Li Ping; Garrabrant, Tom; Lastra, Ricardo R.; Hagemann, Ian S.; Lal, Priti; Feldman, Michael D.; Benencia, Fabián; Coukos, George

doi:10.1038/nm.3541

Cited by 800 publications

(701 citation statements)

References 44 publications

Supporting

Mentioning

666

Contrasting

Unclassified

Order By: Relevance

“…As a consequence, vascular normalization led to an improvement in antitumor T-lymphocyte trafficking and function, and mouse survival [74]. Finally, Motz et al recently showed that VEGF could induce Fas ligand (FasL) expression in tumor endothelial cells, which resulted in inhibition of CTL infiltration into tumors and reduced their cytotoxic activity [75]. …”

Section: Vegf Modulates T-cell Differentiation and Cytotoxic T-cell Funmentioning

confidence: 99%

Rationally Combining Anti-VEGF Therapy with Checkpoint Inhibitors in Hepatocellular Carcinoma

2016

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a fatal disease with rising incidence in the world. For advanced HCC, sorafenib, a multikinase inhibitor, is the only systemic therapy with proven survival benefits. Sorafenib is a pan-VEGF receptor inhibitor, and thus many studies have focused its antivascular effects. But VEGF also acts as an immunosuppressive molecule. VEGF can inhibit maturation of dendritic cells, promote immune suppressive cell infiltration and enhance immune checkpoint molecules expression. On the other hand, potent VEGF inhibition may increase tumor hypoxia, which could hinder antitumor immunity or immunotherapy. Thus, achieving synergy when combining anti-VEGF therapy with immunotherapy may require proper polarization of the tumor microenvironment by dose titration or combination with other immunomodulating agents.

show abstract

Section: Vegf Modulates T-cell Differentiation and Cytotoxic T-cell Funmentioning

confidence: 99%

Rationally Combining Anti-VEGF Therapy with Checkpoint Inhibitors in Hepatocellular Carcinoma

2016

View full text Add to dashboard Cite

show abstract

“…Thus, in these late stages the tumor micro-milieu may frustrate the effector arm of the immune system through different mechanisms. First of all, the influx of tumor-specific T-cells may be hampered by abnormal vascularization [25,26]. In both a xenograft transplant model and an immune refractory spontaneous murine model this problem could be overcome by treatment with low dose of gamma irradiation [25], or by targeting VEGF (vascular endothelial growth factor) [27].…”

Section: Treatment Of Advanced or End-stage Cancer May Fail Due To Immentioning

confidence: 99%

The importance of correctly timing cancer immunotherapy

Nejad

Welters

Arens

et al. 2016

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Introduction:The treatment options for cancer-surgery, radiotherapy and chemotherapy-are now supplemented with immunotherapy. Previously underappreciated but now gaining strong interest are the immune modulatory properties of the three conventional modalities. Moreover, there is a better understanding of the needs and potential of the different immune therapeutic platforms. Key to improved treatment will be the combinations of modalities that complete each other's shortcomings. Area covered: Tumor-specific T-cells are required for optimal immunotherapy. In this review, the authors focus on the correct timing of different types of chemotherapeutic agents or immune modulators and immunotherapeutic drugs, not only for the activation and expansion of tumor-specific Tcells but also to support and enhance their anti-tumor efficacy. Expert opinion: At an early phase of disease, clinical success can be obtained using single treatment modalities but at later disease stages, combinations of several modalities are required. The gain in success is determined by a thorough understanding of the direct and indirect immune effects of the modalities used. Profound knowledge of these effects requires optimal tuning of immunomonitoring. This will guide the appropriate combination of treatments and allow for correct sequencing the order and interval of the different therapeutic modalities. ARTICLE HISTORY

show abstract

“…For example, it was recently shown that tumor endothelium can express FasL, which binds Fas (CD95) to induce cell death. Because cytotoxic CD8 + T cells have higher Fas expression than T regulatory cells (T regs ), FasL expression in the tumor endothelium was inversely correlated with CTL infiltration; such tumors respond better to cancer immunotherapy when used in combination with inhibitors of FasL (74). Thus, characterizing the tumor microenvironment is important for choosing the most promising immunotherapeutic strategies.…”

Section: Tumor Characterizationmentioning

confidence: 99%

Engineering opportunities in cancer immunotherapy

Jeanbart

Swartz

2015

Proc. Natl. Acad. Sci. U.S.A.

115

View full text Add to dashboard Cite

Immunotherapy has great potential to treat cancer and prevent future relapse by activating the immune system to recognize and kill cancer cells. A variety of strategies are continuing to evolve in the laboratory and in the clinic, including therapeutic noncellular (vector-based or subunit) cancer vaccines, dendritic cell vaccines, engineered T cells, and immune checkpoint blockade. Despite their promise, much more research is needed to understand how and why certain cancers fail to respond to immunotherapy and to predict which therapeutic strategies, or combinations thereof, are most appropriate for each patient. Underlying these challenges are technological needs, including methods to rapidly and thoroughly characterize the immune microenvironment of tumors, predictive tools to screen potential therapies in patient-specific ways, and sensitive, information-rich assays that allow patient monitoring of immune responses, tumor regression, and tumor dissemination during and after therapy. The newly emerging field of immunoengineering is addressing some of these challenges, and there is ample opportunity for engineers to contribute their approaches and tools to further facilitate the clinical translation of immunotherapy. Here we highlight recent technological advances in the diagnosis, therapy, and monitoring of cancer in the context of immunotherapy, as well as ongoing challenges.immunoengineering | cancer vaccine | adoptive T-cell therapy | diagnostic tools | checkpoint blockade

show abstract

Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors

Cited by 800 publications

References 44 publications

Rationally Combining Anti-VEGF Therapy with Checkpoint Inhibitors in Hepatocellular Carcinoma

Rationally Combining Anti-VEGF Therapy with Checkpoint Inhibitors in Hepatocellular Carcinoma

The importance of correctly timing cancer immunotherapy

Engineering opportunities in cancer immunotherapy

Contact Info

Product

Resources

About