RNA Biomarkers May Shed Light on Cancer Immunotherapy Response

By David Douglas

April 21, 2020

NEW YORK (Reuters Health) - Long noncoding RNAs (lncRNAs) tied to innate and adaptive immunity in cancer may provide an indication of response to immunotherapy, according to Chinese researchers.

"This study is the first to identify lncRNA as a promising biomarker for molecular classification and prediction of clinical cancer immunotherapy," Dr. Herui Yao of Sun Yat-sen University, in Guangzhou, told Reuters Health by email.

Dr. Yao and colleagues analyzed lncRNA and genomic data on 348 patients with bladder cancer and 71 with melanoma who were treated with immunotherapy during clinical trials. They also included a "pancancer" multicohort of 2,951 patients obtained from The Cancer Genome Atlas (TCGA).

The researchers identified four distinct lncRNA-based immune subtypes with significant differences in immunotherapeutic overall survival (OS) and response.

"Surprisingly," they write, "patients with longer survival were found to have lower expression of immune cells, immune checkpoints, and human leukocyte antigens compared with patients with shorter survival."

The team hypothesized that "immune cells of patients with less survival benefit were in a nonfunctional state."

The greatest OS benefit was in the immune-active subtype characterized by an immune-functional lncRNA signature and high cytotoxic T lymphocyte infiltration. Low versus high lncRNA scores had a significantly longer OS across various cancer types (hazard ratio, 0.32).

Dr. Yao concluded, "Multiomic panels adding lncRNA to the combination of tumor alteration burden, PD-L1 expression, and cytotoxic T lymphocyte infiltration greatly improves the ability to predict benefits of overall survival and response for patients treated with immune checkpoint inhibitor, which could serve as a personalized tool to guide immunotherapy delivery."

The study had no commercial funding, and the researchers report no conflicts of interest.

SOURCE: https://bit.ly/2Kc1AME JAMA Network Open, online April 7, 2020.