Expression of certain immune markers in tumor and surrounding cells can help predict probabilities of recurrence in patients with stage I lung adenocarcinoma, according to new work by researchers at Memorial Sloan-Kettering Cancer Center in New York.
High magnification micrograph of a primary lung adenocarcinoma showing nuclear staining with a TTF-1 immunostain; source: Nephron, Wikimedia CommonsAccording to senior author Prasad S. Adusumilli, MD, the presence of a “good” immune response can apparently help prevent the cancer’s recurrence. In the new study, Adusumilli and colleagues looked for eight tumor-infiltrating immune cells as well as five cytokines in 956 patients with stage I lung adenocarcinoma; the first 478 patients were considered a training cohort, and the second group of 478 was a validation cohort. The results were published online ahead of print on December 26 in the Journal of Clinical Oncology.
Among the immune cells, a high density of FoxP3-positive cells in the tumor-associated stroma was significantly associated with recurrence (P = 0.43 vs low density). The ratio of FoxP3 to CD3 cells was an even stronger predictor, however; the 5-year recurrence-free probability was 85% for those with a high ratio and 77% for those with a low ratio (P = 0.004). This result was replicated from the training cohort to the validation cohort.
Of the cytokines tested, several were found to have prognostic value. Higher expression levels of interleukin-12 receptor beta-2 (IL-12RB2) was associated with better recurrence rates than lower expression, with a 5-year recurrence-free probability of 90% for the former and 80% for the latter (P = 0.026). In contrast, high expression of tumor IL-7R yielded a poorer 5-year recurrence-free probability of 76% vs 86% for those with lower expression of the cytokine (P = 0.001). These results were also replicated in the validation cohort after first appearing in the training cohort. The other three cytokines tested—CCR7, CXCL12, and CXCR4—showed no significant associations with recurrence.
Multivariate analysis showed that these three immune markers—stromal FoxP3-CD3 ratio, IL-12RB2, and IL-7R—are independently associated with recurrence. The FoxP3-CD3 ratio had a hazard ratio (HR) for recurrence of 2.00 (95% CI, 1.22–3.27; P = 0.006). The two cytokines had HRs of 2.24 (95% CI, 1.02–4.95; P = 0.045) and 1.65 (95% CI, 1.02–2.68; P = 0.45), respectively.
The authors wrote that the current system for evaluating of stage I disease relies only on anatomic factors. “In fact, for stage I lung adenocarcinoma, tumor size is the only standard prognosticator available,” they wrote. “In our study, we have demonstrated the prognostic power of immunologic parameters for stage I lung adenocarcinoma.”
Notably, when overall survival was used as an endpoint rather than recurrence, only IL-7R remained a significant prognosticator (P = 0.007). “The ability of IL-7R to prognosticate both recurrence-free and overall survival merits further investigation of its biologic role,” the authors wrote.
