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P05.01 Platelets role in immunotherapy response in non-small cell lung cancer
  1. C Colarusso,
  2. M Terlizzi,
  3. A Pinto and
  4. R Sorrentino
  1. University of Salerno, Fisciano, Italy


Background Immunotherapy has revolutionized the therapeutic landscape of non-small cell lung cancer (NSCLC). In particular, therapy based on immune checkpoint inhibitors (ICIs), such us monoclonal antibodies (mAbs) targeting programmed cell death protein 1 (PD-1) pathway, has changed the survival rate of NSCLC patients. However, a subset of patients is responsive to ICIs and another subset develops acquired resistance to ICIs. In the past few decades, increasing studies have highlighted that high platelets (PLTs) count is associated with poor prognosis of NSCLC patients. Therefore, the aim of this research was to investigate the contribution of PLTs in response to immunotherapy.

Materials and Methods Blood samples from advanced (non-resectable, stage IV) NSCLC patients treated with Atezolizumab were collected at the baseline (T0, prior to the first cycle) and at disease progression (PD). PLTs were isolated by PLT-rich plasma by centrifugation. PD-L1 and Fc gamma receptors (FcγR) PLTs expression were analyzed, and the release of activated PLTs-associated mediators were measured.

Results We found that PLTs count was higher in NSCLC patients at stage IV than earlier stages. These PLTs showed higher levels of PD-L1 than early stages. Moreover, although not in a statistical manner, ICI-non responder NSCLC patients had slightly higher levels of PD-L1. No differences were found in terms of FcγRIII (CD64), FcγRII (CD32) and FcγRI (CD16) expression on isolated PLTs either at baseline or after treatment. In order to better understand whether drug treatment with atezolizumab could alter PLTs activity, the isolated cells were treated in vitro with the mAb (1 µg/mL) to evaluate the release of mediators associated with PLTs activation. We found that differently than healthy PLTs, the stimulation of PLTs derived by NSCLC non-treated patients with Atezolizumab for 30 minutes induced the release of platelet factor 4 (CXCL4). Similarly, the challenge with Atezolizumab was able to trigger the release of TGF-β from NSCLC-derived PLTs after 5 hours of treatment; nevertheless, we observed that PLTs collected from patients who did not respond to treatment (PD) secreted higher amount of TGF-β at earlier time point (1 hour after Atezolizumab addition).

Conclusions Currently simple and robust biomarkers to predict therapy responses towards ICIs are still missing. Our data suggest that the PLTs expression of PD-L1 at PD may reflect the reduced drug efficacy due to the interaction and binding of mAbs (such as Atezolizumab) to the surface PD-L1 by limiting the drug which is not able to exhibit its pharmacological activity on tumor tissues or innate tumor-infiltrated immune cells.

Disclosure Information C. Colarusso: None. M. Terlizzi: None. A. Pinto: None. R. Sorrentino: None.

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