Patients with follicular lymphoma who had disease progression within 24 months of initial diagnosis were found to have lower intratumoral immune infiltration. The study findings were recently reported in the Journal of Clinical Oncology.

The study population included a discovery cohort of 132 patients with early- and advanced-stage follicular lymphoma from a database of patients from Princess Alexandra Hospital and a validation cohort of 138 patients with advanced-stage follicular lymphomphoma who were was treated with rituximab plus cyclophosphamide, vincristine, and prednisolone immunochemotherapy.

A second validation cohort was also used, which included 45 patients with advanced stage follicular lymphoma from the German Low Grade Lymphoma Study Group 2000 trial who were treated with rituximab plus cyclophosphamide, vincristine, doxorubicin, and prednisolone.

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A digital gene expression analysis of 5 immune effector, 6 immune checkpoint, and 1 macrophage molecules revealed clustering of tumor samples, and further analysis identified PD-L2 as the most sensitive and selective immune marker of worse outcomes. 

As a result, PD-L2 was used to stratify patient tumor samples as immune infiltration high or immune infiltration low. Tumor samples designated as immune infiltration high were found to have high amounts of macrophages and expanded T-cell populations. 

Overall, in the discovery cohort, 45.7% of patients with low PD-L2 expression had disease progression within 24 months compared with 16.3% of patients with high PD-L2 expression who had disease progression within 24 months (odds ratio [OR]=4.32; c-statistic=0.81; P=0.001). This finding was also seen in both validation cohorts. 

Between early-stage disease patients and advanced-stage disease patients, no statistically significant difference in PD-L2 expression was seen (P=0.56). The mutation profile between immune infiltration high and immune infiltration low tumor samples was similar, indicating that the mutational profile does not affect the immune infiltration phenotypes.

“Assessment of immune infiltration seems to be a promising tool with which to help identify patients who are at risk for [disease progression within 24 months],” the study authors wrote. 


  1. Tobin JWD, Keane C, Gunawardana J, et al. Progression of disease within 24 months in follicular lymphoma is associated with reduced intratumoral immune infiltration [August 28, 2019]. J Clin Oncol. doi: 10.1200/JCO.18.02365