Targeting the tumor microenvironment of Ewing sarcoma

被引:6
|
作者
Morales, Erin [1 ]
Olson, Michael [2 ,3 ]
Iglesias, Fiorella [4 ]
Luetkens, Tim [5 ,6 ,7 ]
Atanackovic, Djordje [5 ,6 ,7 ]
机构
[1] Univ Utah, Pediat Hematol Oncol Dept, Salt Lake City, UT 84132 USA
[2] Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA
[3] Univ Utah, Huntsman Canc Inst, Hematol & Hematol Malignancies, Salt Lake City, UT 84112 USA
[4] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA
[5] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA
[6] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA
[7] Marlene & Stewart Greenebaum Comprehens Canc Ctr, Baltimore, MD 21201 USA
关键词
cancer vaccines; CAR T cells; chemokines; cytokines; Ewing sarcoma; immune checkpoint inhibition; immune escape; immunosuppression; immunotherapy; microenvironment; monoclonal antibodies; T cells; TCR-transduced T cells; tumor immunology; tumor microenvironment; REGULATORY T-CELLS; MYELOID SUPPRESSOR-CELLS; EMERGING EFFECTOR-CELLS; NITRIC-OXIDE SYNTHASE; CIRCULATING FIBROCYTES; REACTIVE OXYGEN; ANTITUMOR-ACTIVITY; PERIPHERAL-BLOOD; IMMUNE CELLS; II RECEPTOR;
D O I
10.2217/imt-2020-0341
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Lay abstract Ewing sarcoma is an aggressive type of cancer of the bones or soft tissues that mainly affects teenagers. Patients are often treated with intensive treatments which may include chemotherapy in combination with radiation and/or surgery. For patients who present with cancer that has already spread to other sites or that returns after treatment, the cancer can be very hard to cure. This leads to the need for different therapies. Therapies that use the help of the immune system to combat the cancer, called immunotherapies, have had limited success, which is thought to be due to factors in the environment of the tumor that weaken the immune system and so dampen any potential use of it to destroy the cancer cells. We provide an overview of these factors in the tumor environment that allow the cancer cells to escape the immune system; we also discuss potential options to target these factors and, in this way, allow the immunotherapies to destroy the cancer cells more effectively. Ewing sarcoma is an aggressive tumor type with an age peak in adolescence. Despite the use of dose-intensified chemotherapy as well as radiation and surgery for local control, patients with upfront metastatic disease or relapsed disease have a dismal prognosis, highlighting the need for additional therapeutic options. Different types of immunotherapies have been investigated with only very limited clinical success, which may be due to the presence of immunosuppressive factors in the tumor microenvironment. Here we provide an overview on different factors contributing to Ewing sarcoma immune escape. We demonstrate ways to target these factors in order to make current and future immunotherapies more effective and achieve deeper and more durable responses in patients with Ewing sarcoma.
引用
收藏
页码:1439 / 1451
页数:13
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