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Poster Display session 2

3474 - Preselecting tumor-infiltrating lymphocyte subsets to implement adoptive inmmunotherapy in ovarian cancer

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Ovarian Cancer

Presenters

Diego Salas-Benito

Citation

Annals of Oncology (2019) 30 (suppl_5): v403-v434. 10.1093/annonc/mdz250

Authors

D. Salas-Benito1, C. De Andrea2, J.M. Aramendia3, U. Mancheño4, E. Elizalde4, E. Conde4, I. Tamayo4, F. Guillén1, M. Jurado5, J.Á. Mínguez5, A. González Martín6, M. Ponz-Sarvise7, S. Hervás-Stubbs4

Author affiliations

  • 1 Dept. Oncology, Clinica Universitaria de Navarra, 31008 - Pamplona/ES
  • 2 Pathology, Clínica Universidad de Navarra, 31008 - Pamplona/ES
  • 3 Medical Oncology, Clinica Universidad de Navarra, 31008 - Pamplona/ES
  • 4 Immunomodulatory Therapies, Center for Applied Medicine Research, 31008 - Pamplona/ES
  • 5 Gynaecology, Clínica Universidad de Navarra, 31008 - Pamplona/ES
  • 6 Medical Oncology Department, Clínica Universidad de Navarra, 28036 - Madrid/ES
  • 7 Clinical Oncology, Clínica Universidad de Navarra, 31008 - Pamplona/ES

Resources

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Abstract 3474

Background

Adoptive cell therapy (ACT) of expanded in-vitro tumour specific T-cells isolated from fresh tumour infiltrates has shown promising results in melanoma patients, and in ovarian cancer (OC). The use of pre-enriched tumor-specific T cells may simplify the TIL production method and enhances the tumour-reactivity of the final cellular product. We have investigated the role of PD-1 as a biomarker for the isolation and expansion of tumour-specific CD8 TILs in OC.

Methods

Samples from ten OC patients were analyzed. We used flow cytometry FACs Aria sorter for phenotyping and separate T-cells. For reactivity assay we performed co-cultures of TILs with autologous tumour and non-related tumor cell line, and measured INFγ released by ELISPOT. For immunofluorescence multiplex we used a Vectra® microscope and inForm® software to analyzed data. Tumour DNA sequencing was done using a TrueShight™ 170 gene panel.

Results

Both CD8+PD-1+and CD8+PD-1- TIL subsets expanded efficiently and no difference in fold expansion was found. Tumor-reactive TILs were detected in 5/10 patients and this tumor-reactivity was exclusively present in the cells derived from the PD-1+-enriched fraction. There were a higher frequency of CD8+PD-1+CD137+ by FC (p = 0,0079) in reactive group in fresh biopsy. Total CD8+and CD8+PD-1+were more frequent in reactive patients (p = 0,0079, p = 0,0317). CD8+PD-1+CD137+were more frequent (p = 0,0437) by IF in the tumoral epithelium of reactive patients. There were more total CD4+ and CD4+PD-1+by FC in reactive group (p = 0,0079, p = 0,0159). By IF we observed more CD4+PD-1+in both epithelium and stroma of reactive group (p = 0,0437). Patients with reactive TILs exhibited significantly high number of missense mutactions (p = 0,0198).

Conclusions

CD8+PD-1+ T-cell subset include tumour-specific T-cell in OC. CD8+PD-1+CD137+ cells in epithelium may work as a biomarker for reactivity. Higher mutation load is related with tumour-reactive TILs in OC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

ISCIII Spanish grant (PI15/02027).

Disclosure

All authors have declared no conflicts of interest.

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