Background Chronic lymphocytic leukemia (CLL) remains incurable, indicating a need for novel strategies towards disease eradication, including reinvigoration of anti-tumor immune responses. T cells in CLL appear selected by restricted antigens, with recent evidence suggesting that the selecting epitopes may lie within the clonotypic B-cell receptor immunoglobulins (BcR IGs). Here, we present a large-scale evaluation of T cell recognition towards BcR IGs. We predicted MHC-I binding peptides from such clonotypic regions and determined the presence of T cell recognition towards such sequences, using DNA-barcoded multimers of peptide-major histocompatibility complexes (MHC).
Materials and Methods We evaluated 653 peptides derived from the clonotypic BcR IGs of 25 CLL patients across 13 MHC-I alleles based on the MHC-I typing of the patient. We constructed patient-specific peptide-MHC dextran multimers labeled with a unique DNA barcode and a fluorochrome. MHC-multimer binding T cells from PBMC samples where sorted and evaluated through amplification and sequencing of the MHC-attached DNA barcode, to determine the presence of neoepitope reactive T cells.
Results and Conclusion Across the 25 patients we observe T cell reactivity towards 3 peptide-MHC specificities, among the 653 evaluated. The T cell responses observed are listed below:
These response where further validated using conventionally fluorescence labelled pMHC tetramers. This demonstrates that cancer-specific somatic mutation in the BcR IG can be targets of T cell recognition of CLL, and hence serve as targets for novel immunotherapeutic strategies. The level of such T cell recognition was sparse in the cohort evaluated, but could potential be boosted with immunotherapy.
The data to be presented, was in-part presented at the European Hematology Association (EHA) annual meeting.
Disclosure Information Y. Basavaraju: None. A. Vardi: None. A. Agathangelidis: None. N.W. Pedersen: None. M. Karypidou: None. A. Schaap-Johansen: None. A. Fylaktou: None. N. Stavroyianni: None. M. Iskas: None. A. Anagnostopoulos: None. A. Chatzidimitriou: None. P. Marcatili: None. S.R. Hadrup: None. K. Stamatopoulos: None.
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