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Mutation load and an effector T-cell gene signature may distinguish immunologically distinct and clinically relevant lymphoma subsets.

ABSTRACT: Identifying follicular lymphoma (FL) patients with preexisting antitumor immunity will inform precision medicine strategies for novel cancer immunotherapies. Using clinical and genomic data from 249 FL patients, we determined the clinical impact of mutation load and an effector T-cell (Teff) gene signature as proxies for the likelihood of a functional immune response. The FL mutation load estimate varied between 0 and 33 mutations per Mb (median, 6.6), and 92% of FL patients with a high mutation load had high Teff gene expression (P = .001). The mutation load was associated with a benefit from rituximab maintenance: FL patients with low mutation loads experienced a profound benefit from rituximab maintenance (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.15-0.54; P < .001). The Teff gene signature was prognostic as a continuous predictor (P = .008), and was used to separate FL patients into 2 groups, an "inflamed" subset (Teff-high; n = 74) and an "uninflamed" subset (Teff-low; n = 75), with longer progression-free survival (PFS) in the inflamed FL subset (PFS HR, 0.39; 95% CI, 0.21-0.70; P = .002). Furthermore, the subset of inflamed FL tumors demonstrated high expression of other T-cell signatures and counterregulatory genes, which also correlate with PFS. Mutation load and Teff gene expression may help identify immunologically distinct lymphoma subsets relevant for modern immunotherapies.

SUBMITTER: Bolen CR

PROVIDER: S-EPMC5728140 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Mutation load and an effector T-cell gene signature may distinguish immunologically distinct and clinically relevant lymphoma subsets.

Bolen Christopher R CR McCord Ronald R Huet Sarah S Frampton Garrett M GM Bourgon Richard R Jardin Fabrice F Dartigues Peggy P Punnoose Elizabeth A EA Szafer-Glusman Edith E Xerri Luc L Sujobert Pierre P Salles Gilles G Venstrom Jeffrey M JM

Blood advances 20170927 22

Identifying follicular lymphoma (FL) patients with preexisting antitumor immunity will inform precision medicine strategies for novel cancer immunotherapies. Using clinical and genomic data from 249 FL patients, we determined the clinical impact of mutation load and an effector T-cell (T<sub>eff</sub>) gene signature as proxies for the likelihood of a functional immune response. The FL mutation load estimate varied between 0 and 33 mutations per Mb (median, 6.6), and 92% of FL patients with a hi ...[more]

PMID: 29296835

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Dataset Information

Mutation load and an effector T-cell gene signature may distinguish immunologically distinct and clinically relevant lymphoma subsets.

Publications

Mutation load and an effector T-cell gene signature may distinguish immunologically distinct and clinically relevant lymphoma subsets.

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