Immunotherapy
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.

Immunomodulators

• 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.