A groundbreaking study has recently identified a cluster of 140 genes that may serve as a predictive tool for improved disease-free survival among patients grappling with non-small cell lung cancer (NSCLC) undergoing a combined treatment of immunotherapy and low-dose radiation. Published in Cell Reports Medicine, the findings propose that this distinctive “gene signature” could delineate a subgroup of lung tumors with a higher likelihood of being eradicated by immunotherapies.
While immunotherapy has been hailed for its life-saving potential, only a fraction of patients—ranging from 20 to 25 percent—respond positively to this treatment regimen, which stimulates the body's own immune system to combat cancer cells. Anticipating which patients would benefit from such an approach, and understanding the underlying mechanisms, could offer a beacon of hope for individuals who have exhausted conventional treatment avenues, including chemotherapy.
In a meticulous examination of 60 patients diagnosed with NSCLC, the research team had previously established that supplementing a course of durvalumab, an immune-enhancing medication, with a low dose of radiation significantly enhanced cancer-free survival rates in a majority of the cohort. To unravel the reasons behind the lack of response in some tumors to this therapeutic regimen, the investigators scrutinized pretreatment tumor biopsies from the study participants.
By scrutinizing the gene expression profiles, the researchers discerned the specific genes that were upregulated and downregulated in each biopsy sample. They juxtaposed the gene expression profiles of ten tumors achieving major pathologic response (MPR)—defined by the elimination of over 90 percent of cancer cells in patients' tumors—with those of six tumors that did not exhibit such a response to the combination treatment.
Their analysis revealed that the two subsets of pretreatment tumors could be reliably distinguished by a distinct set of genes, comprising 135 genes that were upregulated and 5 genes that were downregulated. Notably, a majority of the 135 upregulated genes were associated with heightened cell growth, hinting at the aggressive nature of tumors responsive to the dual therapy.
Furthermore, the researchers delved into the dynamic changes in gene expression profiles before and after treatment in the responsive cancers. They observed that in tumors demonstrating MPR, the dual therapy not only counteracted the activity of this 140-gene set but also bolstered the activation of genes linked with immune response and tissue repair pathways.
The activity exhibited by the 140 genes correlating with treatment response holds immense promise, as clinicians could leverage this signature to pinpoint individuals poised to derive maximal benefits from immunotherapy.
Looking ahead, the researchers intend to validate whether tumors harboring this aggressive gene signature manifest a more favorable response to the combination therapy in a larger patient cohort, paving the way for personalized treatment strategies in NSCLC management.
Source: Weill Cornell Medical College