1063P - Anti-PD1 therapy effects on T cell repertoire and functions in patients with NSCLC cancer: a preliminary study to identify biomarkers of efficacy

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Translational Research
Presenter Giusi Barra
Citation Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378
Authors G. Barra1, G. Pasquale2, C.M. Della Corte3, F. Papaccio4, M. Orditura5, F. De Vita5, F. Ciardiello5, R. De Palma1, F. Morgillo5
  • 1Clinical Immunology, AOU Seconda Università degli Studi di Napoli (AOU-SUN), 80131 - Napoli/IT
  • 2Clinical Immunology, AOU Seconda Università degli Studi di Napoli (AOU-SUN), Napoli/IT
  • 3Medical Oncology, AOU Seconda Università degli Studi di Napoli (AOU-SUN), Napoli/IT
  • 4Medical Oncology, AOU Seconda Università degli Studi di Napoli (AOU-SUN), 80131 - Napoli/IT
  • 5Medical Oncology, AOU Seconda Università degli Studi di Napoli (AOU-SUN), 81130 - Napoli/IT

Abstract

Background

Immune responses have a pivotal role in protecting against tumors, since conventional chemotherapy may effectively treat cancer but its efficacy is compromised by tumor relapse. Chemotherapy “per se” can have immunostimulatory effects, and the ability to sustain an antitumor T cell response activate host immunity and prevent tumor re-growth. Anti-PD1 antibodies may be used in clinics to boost immune responses through the blocking of an inhibitor receptor on T cells. Here, we evaluate the T cell repertoire and cytokines in five NSCLC patients who underwent anti-PD1 therapy after chemotherapy.

Methods

We used PBMC to study T cell repertoire by a PCR based technique discriminating clonotype length and nucleotide sequences, and cytokine production. RNA and cDNA were prepared from PBMC of patients, and the different families of T cell receptors were amplified and sequenced with specific primers. The message for ɣ-IFN, IL-2, IL-4, IL-12, IL-13 and IL-17 was studied by Quantitative PCR. Presence of cytokine message was confirmed measuring the protein in the serum. Each patient was studied at the end of chemotherapy and after each anti-PD1 shot.

Results

We found that chemotherapy shaped a specific T cell repertoire in these patients, expanding several T cell clonotypes. Importantly, the T cell clonotypes expanded upon chemotherapy were often maintained by anti-PD1 administration undergoing a long-lasting expansion. Production of cytokines was fluctuating during therapy with anti-PD1 and we observed a subversion of cytokine profile. To note, a prolonged effect in term of clinical outcome was paired with a consolidated production of IL-12 and ɣ-IFN.

Conclusions

These data show that chemotherapy reshapes a specific T cell repertoire possibly involved in antitumor response, and the functional profile of these cells marked a prolonged efficient anti-tumor T cell response. Although these are preliminary data, these results pave the ground to better understand how to study and monitor the patients undergoing therapy with anti immune checkpoints. This is of critical importance due to the need to identify biomarkers and monitoring tools to optimize the use of these drugs, also in light of the high costs of these therapies.

Clinical trial identification

Legal entity responsible for the study

Dept. of Clinical & Experimental Medicine, Second University of Naples

Funding

Dept. of Clinical & Experimental Medicine, Second University of Naples

Disclosure

All authors have declared no conflicts of interest.