Study suggests how existing and emerging immunotherapy treatments could be successful for sarcomas

Sarcomas - cancers of the connective tissues like muscles, joints, fat and bone -; come in dozens of subtypes. Clinical trial results have been mixed when treating these diverse tumors with immunotherapy, a targeted therapeutic strategy that has success in other cancers.

But now a study to be published May 2 in the journal Cancer suggests how both existing and emerging immunotherapy treatments could be successful for sarcomas.

Two sarcoma subtypes -; leiomyosarcoma and pleomorphic -; showed biological characteristics suggesting they are susceptible to an existing immunotherapy approach known as checkpoint inhibitors. This treatment works by blocking a protein that keeps immune cells from attacking cancerous cells.

"Checkpoint inhibitors have transformed the standard of care for melanoma and lung cancer, but it's been tough to make headway in developing immunotherapy strategies for sarcomas," said Dr. Seth Pollack, a clinical researcher at Fred Hutchinson Cancer Research Center and the study's senior author. "Before this study, we had a feeling based on preliminary data that some of the sarcomas would behave very differently based on the immune response, and these findings suggest that we're on the right track."




- expression of 760 genes, mainly related to immune function;




Leiomyosarcoma and pleomorphic sarcomas were the two subtypes that had a greater immune response by nearly all of the measures in the study, which means that they're more visible to the immune system.

"To me, these findings say that there are certain sarcoma subtypes that really lend themselves to the development of checkpoint inhibitor-based strategies," Pollack said. Checkpoint inhibitors are immunotherapies that remove the PD-1 "off switch" and essentially allow the immune system to attack cancer more aggressively.


"It's too early to change how doctors will treat patients, but these findings are influencing the design of clinical trials in sarcoma," Pollack said.


"Our results show that even though other studies have been unclear about whether checkpoint inhibitors work for leiomyosarcoma, that there's still a way to make them work for this subtype and that we need to keep working on it," Pollack said.

Pollack is conducting ongoing clinical trials combining chemotherapies and checkpoint inhibitors:


Sarcomas comprise about 1 percent of all cancers; about 20,000 people a year are diagnosed each year in the United States with one of its many subtypes. Though sarcomas are often called "rare," Pollack said that's a misnomer.




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