Adoptive T-cell transfer is a promising approach to cancer immunotherapy. It’s efficiency essentially depends on the extent of tumor-specific T-cell enrichment within the graft that can be estimated via activation with identifiable neoantigens, tumor-associated antigens (TAAs), or living or lyzed tumor cells. However, corresponding approaches remain laborious, time-consuming, and functionally limited, hampering clinical development. We believe that our approach to the rapid assessment of tumor-specific TCRs enrichment should fuel the T-cell therapy development. Here we demonstrate that homology cluster analysis of T-cell receptor (TCR) repertoires efficiently identifies tumor-reactive TCRs, allowing to: 1) detect their presence among tumor-infiltrating lymphocytes (TILs); 2) optimize TIL culturing conditions, with IL-2low/IL-21/anti-PD-1 combination showing increased efficiency; 3) investigate surface marker-based enrichment for tumor-targeting T-cells in freshly isolated TILs (enrichment сonfirmed for CD4+/PD-1+/CD39+ and CD8+/PD-1+/CD39+ subsets), or re-stimulated TILs (informs on enrichment in 4-1BB-sorted cells).
The datasets represented here display pre-processed TCR-beta repertoires of tumor-infiltrating lymphocytes from metastasized lymph nodes of melanoma patients.
cDNA libraries were generated using the Human RNA TCR Multiplex kit (MiLaboratories). We aimed to achieve coverage of 20 paired-end reads per cell for sorted and cultivated TIL populations and approximately 2*10^6 reads per tumor sample fragment. Sequencing was performed using Illumina NextSeq platform (2 х 150 bp read length).
Raw sequencing data fastq data was processed with MiXCR software (MiLaboratories). TCR repertoires were extracted using VDJtools v. 1.2.1.
Cloneset tables are in VDJtools software format: tab-delimited text files.
Cite items from this project
DataCiteDataCite
3 Biotech3 Biotech
3D Printing in Medicine3D Printing in Medicine
3D Research3D Research
3D-Printed Materials and Systems3D-Printed Materials and Systems
4OR4OR
AAPG BulletinAAPG Bulletin
AAPS OpenAAPS Open
AAPS PharmSciTechAAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität HamburgAbhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)ABI Technik (German)
Academic MedicineAcademic Medicine
Academic PediatricsAcademic Pediatrics
Academic PsychiatryAcademic Psychiatry
Academic QuestionsAcademic Questions
Academy of Management DiscoveriesAcademy of Management Discoveries
Academy of Management JournalAcademy of Management Journal
Academy of Management Learning and EducationAcademy of Management Learning and Education
Academy of Management PerspectivesAcademy of Management Perspectives
Academy of Management ProceedingsAcademy of Management Proceedings
Academy of Management ReviewAcademy of Management Review