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Immunoprofiling and survival in DLBCL
been tested in phase I trials for the patients with relapsed/refractory DLBCL with promising results.34,35 However, in comparison to Hodgkin lymphoma, and according to a recently reported phase II trial with relapsed/refractory DLBCL, response rates to single agent PD1 blockade are low.36 It is possible that lower incidence and magnitude of 9p24.1 alterations translating to lower PD-L1 expression in tumor cells in comparison to classic
Hodgkin lymphoma explains at least to some extent why the majority of the DLBCL patients do not benefit from single agent checkpoint blockade. Another explanation may be that the non-immune mechanisms or alternative immune checkpoints are upregulated and thereby have more clinical impact in DLBCL. Our results suggest that blockade of TIM3 and/or LAG3 might be beneficial in DLBCL patients with immune checkpoint expressing
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Figure 6. The impact of immune checkpoint molecules and distinct T-cell subtypes on survival. (A and B) Forest plots visualizing the impact of T cells and their immunophenotypes on overall survival (OS) in months (mo) in the Nordic Lymphoma Group (NLG) Trial (A) and Helsinki diffuse large B-cell lymphoma study (HEL- DLBCL) (B) cohorts, as evaluated using Cox univariate tests with continuous variables. (C-H) Kaplan-Meier plots (log-rank test) visualizing survival associations of dis- tinct TIM3+ cell subpopulations. Cut-off was set at the highest expressing one-third versus the lowest expressing two-thirds.
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