Introduction: Targeted therapies may induce anti-tumor immune activation in r/r-TCL. We evaluated serial immunologic changes in patients with r/r-TCL treated on the phase 1 RAdR trial (NCT04447027).
Methods: Patients with r/r-TCL received up to 6 cycles of RAdR. Peripheral blood was collected prior to each cycle and circulating immune cells were characterized by spectral flow cytometry using a 30-marker panel.
Objectives: Evaluate the baseline immunologic profile and dynamic changes in r/r-TCL stratified by response to targeted therapy.
Results: Baseline levels of NK-cell were similar in responders (N=10) and non-responders (N=5) but increased with treatment in responders; mean 90.5 NK-cells/uL at cycle 1, 143.9 at cycle 2 and 195 at cycle 5 (p< 0.05). NK-cells decreased in non-responders, 88 NK-cells/uL at cycle 1 and 67.5 at cycle 2 (p=0.22). This NK cell expansion in responders included both cytokine-producing (CD56brightCD16-) and cytotoxic (CD56dimCD16+) NK cells which co-expressed perforin/granzyme-B. At baseline, levels of NKG2D+ NK and T-cells were significantly higher in non-responders compared to responders (p< 0.05). Interestingly, NKG2D+ NK and CD8 T-cells increased in responders and decreased in non-responders after 1 cycle of RAdR. Persistent increases in cytotoxic and cytokine producing NK-cells were observed at cycle 4 in responders (p< 0.05). Unsupervised analysis demonstrate these activated NK-cells also co-express OX40, CD57, and Eomes.
Conclusions: The baseline activation state of NK-cells, and both acute and long-term NK-cell expansion and activation follow distinct patterns in responders and non-responders to RAdR. Combination with monoclonal antibodies or NK-cell based immunotherapies are rationale therapeutic strategies to improve RAdR like regimens.
