A multifactorial model of T cell expansion and durable clinical benefit in response to a PD-L1 inhibitor

13Citations
Citations of this article
54Readers
Mendeley users who have this article in their library.

Abstract

Checkpoint inhibitor immunotherapies have had major success in treating patients with late-stage cancers, yet the minority of patients benefit. Mutation load and PD-L1 staining are leading biomarkers associated with response, but each is an imperfect predictor. A key challenge to predicting response is modeling the interaction between the tumor and immune system. We begin to address this challenge with a multifactorial model for response to anti-PD-L1 therapy. We train a model to predict immune response in patients after treatment based on 36 clinical, tumor, and circulating features collected prior to treatment. We analyze data from 21 bladder cancer patients using the elastic net high-dimensional regression procedure and, as training set error is a biased and overly optimistic measure of prediction error, we use leave-one-out cross-validation to obtain unbiased estimates of accuracy on held-out patients. In held-out patients, the model explains 79% of the variance in T cell clonal expansion. This predicted immune response is multifactorial, as the variance explained is at most 23% if clinical, tumor, or circulating features are excluded. Moreover, if patients are triaged according to predicted expansion, only 38% of non-durable clinical benefit (DCB) patients need be treated to ensure that 100% of DCB patients are treated. In contrast, using mutation load or PD-L1 staining alone, one must treat at least 77% of non-DCB patients to ensure that all DCB patients receive treatment. Thus, integrative models of immune response may improve our ability to anticipate clinical benefit of immunotherapy.

Cite

CITATION STYLE

APA

Leiserson, M. D. M., Syrgkanis, V., Gilson, A., Dudik, M., Gillett, S., Chayes, J., … Mackey, L. (2018). A multifactorial model of T cell expansion and durable clinical benefit in response to a PD-L1 inhibitor. PLoS ONE, 13(12). https://doi.org/10.1371/journal.pone.0208422

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free