ABSTRACT
BACKGROUND: Adoptive immunotherapy with tumour-infiltrating lymphocytes (TIL) may benefit from the use of selective markers, such as PD-1, for tumour-specific T-cell enrichment, and the identification of predictive factors that help identify those patients capable of rendering tumour-reactive TILs. We have investigated this in ovarian cancer (OC) patients as candidates for TIL therapy implementation. METHODS: PD-1- and PD-1+ CD8 TILs were isolated from ovarian tumours and expanded cells were tested against autologous tumour cells. Baseline tumour samples were examined using flow cytometry, multiplexed immunofluorescence and Nanostring technology, for gene expression analyses, as well as a next-generation sequencing gene panel, for tumour mutational burden (TMB) calculation. RESULTS: Tumour-reactive TILs were detected in half of patients and were exclusively present in cells derived from the PD-1+ fraction. Importantly, a high TIL density in the fresh tumour, the presence of CD137+ cells within the PD-1+CD8+ TIL subset and their location in the tumour epithelium, together with a baseline T-cell-inflamed genetic signature and/or a high TMB, are features that identify patients rendering tumour-reactive TIL products. CONCLUSION: We have demonstrated that PD-1 identifies ovarian tumour-specific CD8 TILs and has uncovered predictive factors that identify OC patients who are likely to render tumour-specific cells from PD-1+ TILs.
Subject(s)
Biomarkers, Tumor/genetics , CD8-Positive T-Lymphocytes/immunology , Gene Expression Regulation, Neoplastic , Lymphocytes, Tumor-Infiltrating/immunology , Ovarian Neoplasms/pathology , Programmed Cell Death 1 Receptor/metabolism , Biomarkers, Tumor/metabolism , Female , Follow-Up Studies , Humans , Ovarian Neoplasms/genetics , Ovarian Neoplasms/immunology , Phenotype , Prognosis , Retrospective StudiesABSTRACT
Introducción. La conización con asa diatérmica (loop electro excision procedure) es un procedimiento diagnóstico y terapéutico simple y de uso extendido en lesiones cervicales. Es generalmente empleado de forma ambulatoria bajo anestesia general. Sujetos y métodos. Describimos el hallazgo de un caso de invasión linfovascular en la conización de una lesión intraepitelial escamosa de alto grado de cérvix. Conclusiones. A pesar de la controversia creada en torno al significado pronóstico de la invasión linfovascular, su presencia excluye el tratamiento conservador (AU)
Background. The loop electro excision procedure is a simple and widely used diagnostic and therapeutic technique in cervical lesions. This procedure is usually performed in the ambulatory setting under local anaesthesia. Subjects and methods. We describe a case of lymphovascular space invasion detected in the cone biopsy of a high-grade squamous intraepithelial lesion of the cervix. Conclusions. Although the prognostic significance of LVSI is controversial, its identification precludes conservative treatments (AU)
