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  • 08.03 MHJC-based large-scale screening of anti-tumor T cells in chronic lymphocytic leukemia reveals CD8+ T cells with specificity against the clonotypic B-cell receptor immunoglobulin

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Oral Presentations
Plenary symposium 8: ‘lost in translation’
08.03 MHJC-based large-scale screening of anti-tumor T cells in chronic lymphocytic leukemia reveals CD8+ T cells with specificity against the clonotypic B-cell receptor immunoglobulin
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  1. Y Basavaraju1,
  2. A Vardi2,3,
  3. A Agathangelidis2,
  4. NW Pedersen1,
  5. M Karypidou2,
  6. A Schaap-Johansen1,
  7. A Fylaktou4,
  8. N Stavroyianni3,
  9. M Iskas3,
  10. A Anagnostopoulos3,
  11. A Chatzidimitriou2,
  12. P Marcatili1,
  13. SR Hadrup1 and
  14. K Stamatopoulos2
  1. 1Denmark Technical University, Lyngby, Denmark
  2. 2Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece
  3. 3Hematology Department and HCT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece
  4. 4National Peripheral Histocompatibility Center, Department of Immunology, Hippokration Hospital, Thessaloniki, Greece

Abstract

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:

View this table:

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.

https://doi.org/10.1136/jitc-2022-ITOC9.5

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