For Sarcoma

How is Immunotherapy for Sarcoma Changing the Outlook for Patients?

Reviewed by:

Corrie Painter, PhD
Broad Institute of MIT and Harvard

Immunotherapy for sarcoma has some success cases, including the earliest known instances of spontaneous regression, although sarcoma cancer immunology is still largely unknown.

A cancer of the body’s connective tissues, including muscle, fat, bone, and cartilage, sarcomas are categorized and named based on the type of tissue that they resemble.

Some prominent sarcomas include:

  • osteosarcoma, which resembles bone
  • chondrosarcoma, which resembles cartilage
  • liposarcoma, which resembles fat
  • leiomyosarcoma, which closely resembles smooth muscle

Sarcoma is a rare cancer in adults and accounts for just 1% of all cancer diagnoses in the United States, where there will be an estimated 17,000 new cases and 7,000 deaths in 2023. Worldwide, the most common form of this cancer type is Kaposi’s sarcoma, which was diagnosed in an estimated 42,000 people and caused about 20,000 deaths in 2018. Another of the most common forms of this cancer type, gastrointestinal stromal tumor (GIST), affects between 4,000-6,000 people in the United States per year. Chordoma, a rare cancer that is diagnosed in one in one million people globally every year, occurs along the spine and gradually enters the bone and soft tissue around the tumor.

Sarcoma is more prevalent in children, representing approximately 15% of all childhood cancer cases, with more aggressive bone sarcomas, such as Ewing sarcoma, occurring much more frequently in children than in adults.

Many patients treated with conventional therapies (surgery, chemotherapy, and radiation) will develop advanced, metastatic sarcomas that are resistant to those approaches, so new treatments are needed.

Sarcoma Cancer Treatment Options

Surgery is imperative to the treatment of most types of sarcomas, and additional chemotherapy or radiation therapies may be applied before and/or after surgery. In the case of many bone sarcomas, chemotherapy significantly and positively impacts the prognosis for sarcoma patients, though the treatment process is a long and arduous one.

While effective in some sarcomas, between 25-50% of sarcoma patients treated with conventional methods will still develop metastatic disease. In these cases in which the cancer has spread to other organs, complete responses to chemotherapy are quite rare. Fortunately, immune-based treatments, collectively known as immunotherapy, have helped against other advanced cancers and have begun to show benefits in certain types of advanced sarcoma.

Currently, there are three FDA-approved immunotherapy options for patients with sarcoma, and many more are being investigated in clinical trials.


  • Atezolizumab (Tecentriq®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for upsets of patients with alveolar soft part sarcoma (ASPS)
  • Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced sarcoma that has DNA mismatch repair deficiency (dMMR)
  • Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced sarcoma that has high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H)

Targeted Antibodies

  • Denosumab (Xgeva®): a monoclonal antibody that targets the RANKL pathway; approved for subsets of patients with bone cancer

Several other immunotherapies have shown effectiveness in clinical trials and could become approved for patients in the near future.

CRI’s Impact in Sarcoma

At the Cancer Research Institute, we work to advance immune-based therapies for the treatment of all types of sarcomas. Since 1997, our organization has provided more than $2.6 million of funding in support of sarcoma research, including studies of adoptive immunotherapy with genetically engineered CD8+ T cells used to induce tumor regressions, clinical trials of adoptive cell therapies and immune checkpoint inhibitors for synovial sarcoma and mixed round cell liposarcoma, and T cell-dependent cancer immunoediting.

  • In 2011, Steven A. Rosenberg, Mark Dudley (1993-1996 CRI postdoctoral fellow), and colleagues at the Surgery Branch of the National Cancer Institute demonstrated that adoptive immunotherapy with CD8+ T cells that were genetically engineered to recognize the NY-ESO-1 antigen could induce significant tumor regressions in patients with metastatic synovial sarcoma and melanoma.
  • CRI has partnered with Stand Up To Cancer (SU2C) to fund a “Dream Team” of researchers working to develop the next frontier of cancer immunotherapy, including an adoptive cellular therapy plus immune checkpoint inhibitor trial for the treatment of NY-ESO-1+ sarcomas.
  • In 2012, using a sarcoma model, Robert D. Schreiber (CLIP grantee and Scientific Advisory Council member), Matthew Vesely (CRI predoctoral fellow), and their colleagues revealed a T cell-dependent mechanism of cancer immunoediting.
  • In 2019, CRI and the Chordoma Foundation established a research partnership to advance treatment options for chordoma and the first grant was awarded to Cassian Yee, MD

See what sarcoma-specific research we’re currently funding. With your help, we can fund more research and revolutionize the way sarcoma is treated forever—curing more people and saving more lives.

Related Links

Sarcoma Statistics

1.7% Of all new cancer diagnoses in the U.S. are sarcoma

83% 5-year survival rate for patients with localized sarcoma

17k Newly diagnosed patients each year in the United States

Sarcoma Clinical Trial Targets

Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new cancer treatments. Use this information to consider your clinical trial options.

Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers on cancer cells, in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in sarcoma clinical trials include:

  • CD52: a protein found on the surface of mature immune cells as well as other cell types
  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • PDGFRα: a surface receptor that plays a role in stimulating cell division and growth
  • RANKL: a protein that plays a role in bone regeneration and modeling, and is often overexpressed in cancer
  • VEGF/VEGF-R: a pathway that can promote blood vessel formation in tumors

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in sarcoma clinical trials include:

  • NY-ESO-1: a protein that is normally produced only before birth, but is often abnormally expressed in cancer
  • P53: a tumor suppressor protein that is often mutated, nonfunctional, and overexpressed in cancer
  • Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels
  • WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)

Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in sarcoma clinical trials include:

  • Epstein-Barr Virus (EBV)-related antigens: foreign viral proteins expressed by EBV-infected cancer cells
  • GD2: a pathway that controls cell growth, adhesion, and migration, and is often abnormally overexpressed in cancer cells
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • NY-ESO-1: a protein that is normally produced only before birth, but is often abnormally expressed in cancer

Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in sarcoma clinical trials include:

  • CD47: this surface protein acts as a “don’t eat me!” signal that protects cancer from being consumed by certain immune cells; blocking CD47 can improve their cancer-eating activity
  • CD73 or A2AR: blocking these pathways can help prevent the production of immunosuppressive adenosine
  • CSF1/CSF1R: blocking this pathway can help reprogram cancer-supporting macrophages
  • CTLA-4: blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
  • IDO: blocking this enzyme’s activity can help prevent cancer-fighting T cells from being suppressed
  • IL-2/IL-2R: activating this cytokine pathway can help promote the growth and expansion of cancer-fighting T cells
  • LAG3: blocking this pathway may be able to help prevent suppression of cancer-fighting T cells
  • PD-1/PD-L1: blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted,” and can restore the activity of already-exhausted T cells
  • Toll-like receptors (TLRs): activation of these innate immune receptors can help stimulate vaccine-like responses against tumors

Oncolytic virus therapy uses viruses that are often, but not always, modified in order to infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in sarcoma clinical trials include:

  • Herpes simplex virus: a virus that can cause the formation of sores on the mouth and genitals
  • Vaccinia virus: the virus that was used to help vaccinate against and eliminate smallpox; rarely causes illness in humans and is associated with a rash covering the body

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