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. (21st September 2022)

• Record Type: Journal Article
• Authors: Basavaraju, Y; Vardi, A; Agathangelidis, A; Pedersen, NW; Karypidou, M; Schaap-Johansen, A; Fylaktou, A; Stavroyianni, N; Iskas, M; Anagnostopoulos, A; Chatzidimitriou, A; Marcatili, P; Hadrup, SR; Stamatopoulos, K
• Is Part Of: Journal for immunotherapy of cancer. Volume 10(2022)Supplement 1
• Page Start: A3
• Page End: A3
• Publication Date: 2022-09-21
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2022-ITOC9.5
• Languages: English
• ISSNs: 2051-1426

Abstract

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: 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.