Immune checkpoint modulation is a promising treatment strategy in HNSCC. PD-1 inhibition is currently studied in combination with conventional oncologic treatments. However, the impact of curative conventional treatment (surgery, (chemo-)radiotherapy (CRT)) on the expression of targetable ICM has not been studied previously.
In a prospective non-interventional immune monitoring trial (Immune Response Evaluation to curative Conventional Therapy; IRECT; NCT03053661) peripheral blood mononuclear cells (PBMC) from 22 patients with HNSCC were collected at 8 pre-specified time points during curative conventional treatment (baseline, post-surgery, mid-CRT, end of CRT, 3-, 6-, 9-, 12-months post end of treatment (EOT)). PBMC were analyzed by flow cytometry. Nine ICM (PD1, CTLA4, BTLA, CD137, CD27, GITR, OX40, LAG3, TIM3) were determined in different immune cell subsets (CD8, CD4, CD19, CD39 Treg) over the course of treatment.
Paired samples tests revealed significant changes compared to pre-treatment samples. Compared to baseline, surgery had no significant impact on ICM expression. Median CD8/PD1 were significantly lower at 3 and 6 months post EOT, CD4/PD1, CD19/PD1 and Treg/PD1 were significantly higher at the end of CRT, whereas Treg/PD1 were significantly lower at 3 and 6 months post EOT. CD8/BTLA were significantly decreased from mid-CRT until 12 months post EOT, whereas CD4/BTLA and Treg/ BTLA were significantly decreased from 3 to12 months post EOT. CD4/CD27 were significantly lower from mid-CRT until 12 months post EOT, whereas CD19/CD27 and Treg/CD27 were significantly decreased from 3 to 12 months post EOT. CD4/OX40 and Treg/OX40 increased mid-CRT until 3 months post EOT, but significance was not confirmed after correcting for multiple testing.
Whereas surgery alone seems not to alter ICM expression, CRT has a significant impact on the expression of PD1, BTLA and CD27. OX40 seems to increase during CRT. These results reveal a rational for the combination of PD1 inhibitors with CRT. Combining such a treatment with OX40 inhibitors may be a promising strategy.
Clinical trial identification
Legal entity responsible for the study
University Medical Center Ulm.
Deutsche Forschungsgemeinschaft (GRK2254).
T.K. Hoffmann: Advisory board member: Merck Sharp & Dohme; Lecture fees: Merck Sharp & Dohme, Merck Serono. P.J. Schuler: Advisory board member: Bristol Myers Squibb. S. Laban: Advisory board member: AstraZeneca, Merck Sharp & Dohme; Lecture fees: Bristol-Myers Squibb, Merck Serono. All other authors have declared no conflicts of interest