By Deborah Borfitz
January 25, 2021 | Oncologists have increasingly relied on the immune cell makeup of tumors to better estimate patient outcomes and response to therapy. For most types of cancers, a higher immune content is a good sign. But, for unknown reasons, the opposite is true for men with more aggressive forms of prostate cancer whose tumors are rich with immune cells.
Now, Moffitt Cancer Center researchers have discovered a way to pinpoint this subset of high-risk patients who may benefit from combined immune-radiotherapy modalities. The answer gets computed from a combination of the immune content score (ICS) and the 22-gene Decipher classifier score that is predictive of metastasis, according to Kosj Yamoah, M.D., Ph.D., associate member and director of cancer disparities research in the departments of radiation oncology and cancer epidemiology.
Yamoah led a study, newly published is European Urology (DOI: 10.1016/j.eururo.2020.11.038), which describes the combined approach for genomic risk stratification for prognosis and treatment selection for grade group 4 and 5 prostate cancer patients. Clinical trials are already underway to verify the results in a phase 2 study of African American and non-African American men with localized prostate cancer, using an updated version of Decipher (developed by Decipher Biosciences) that provides additional information on the immune content of tumor tissues at diagnosis.
The practical application of this body of work is in addressing localized to semi-advanced prostate cancer that has not spread beyond the pelvis, he adds, to remove the “bad actor” driving metastasis.
The Decipher test was developed from samples derived mainly from men of European origins, and although the molecular pathways to prostate cancer do not necessarily differ by ethnicity, the predominant immune-rich pathway may not be the same across patient populations, Yamoah continues.
Overall, up to one-quarter of all prostate cancer patients have a high ICS that puts them at particularly high risk for aggressive disease. But the figure is closer to one-third for men of African descent, he says, so they stand to benefit even more from enhanced treatment.
The findings open the potential for therapies targeting the dysfunctional immune cells seen present in the microenvironment of some particularly lethal prostate tumors, he says. They also make the routinely used Decipher Genomics Resource Information Database (GRID) platform more “clinically meaningful” by not only singling out patients who are high risk but also those with an immune profile that makes them good candidates for combined immunotherapy and radiotherapy.
The research team analyzed data from 8,071 prostate cancer patient samples of all disease grades in the Decipher GRID registry and gave each an ICS derived from the mean expression of 264 immune cell-specific genes, says Yamoah. The samples were then separated into four immunogenomic subsets based on whether the ICS and Decipher scores were high or low.
As it turned out, about 25% of all grade 4/5 patient samples fell in the ICS high/Decipher high subset. This same group had a higher abundance of T cells and monocyte/macrophages and may respond well to radiation therapy.
That the subpopulation of aggressive tumors with a high immune score seems to have a high radiation sensitivity is a “win-win scenario,” comments Yamoah. Besides killing the cancer, a secondary benefit of radiation is that it generates antigens that in turn engage the immune system in the counterattack.
The combination of radiation and immunotherapy functions much like a vaccine, prompting the body to create antibodies to help fight disease. The beauty of using the Decipher genomic platform is that it is already in routine use and therefore the subtyping methodology could translate to the clinic without undue delay.