NorthWest Biotherapeutics Inc (NWBO)

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The UCLA paper itself demonstrated TIL count is a predictive biomarker for DCVax-L therapy, but not predictive of SOC effect upon GBM. It's an important insight.

In conclusion, estimated TIL content may be used as a predictor of clinical response and way to select patients for DC vaccination therapy.
cancerimmunolres.aacrjournals.org/content/early/2016/03/11/2326-6066.CIR-15-0240

We determined that the estimated TIL content of pretreatment tumor directly correlated with survival and was predictive of which patients would benefit from the therapy.

We then correlated the estimated TIL content with TTP and OS in our patient population. The estimated TIL count of glioblastomas, prior to DC vaccination, was the most significant predictor of outcome in our patient population. Cox regression analyses demonstrated that higher estimated TIL content in the pretreatment tumor was a strong predictor of longer TTP (HR=0.252, 95% CI=0.066-0.965, p=0.0442) and OS (HR=0.277, 95% CI=0.078–0.978, p=0.0461, Supplementary Table S3) in GBM patients who received DC vaccination.

In order to assess whether the prognostic role of TILs may be independent of DC vaccination, we performed TCR sequencing on an additional six GBM patients who did not receive immunotherapy (3 newly diagnosed and 3 recurrent GBM samples). To account for spatial TIL heterogeneity within the tumors, we also collected three different pieces of tumor for genomic DNA analysis. In these patients who did not receive immunotherapy, the estimated TIL content did not significantly correlate with TTP (HR=1.258; p=0.835) nor OS (HR=1.260; p=0.837; Supplementary Figure 2), suggesting that the prognostic benefit of TIL is specifically relevant for patients who subsequently go on to receive immunotherapy.

We showed that an increased estimated TIL content prior to therapy was associated with prolonged TTP and OS. All very long-term survivors in this trial had estimated TIL content in the top quartile. The correlations between estimated TIL content and TTP and OS argues that estimated TIL content in the initial tumor specimen may be used to select patients for DC vaccination and may be applicable to other immunotherapies as well. In contrast, TIL content was not associated with survival in patients who were not treated with immunotherapy.

A significant correlation was found between a higher estimated TIL content and increased time to progression (TTP) and overall survival (OS).