Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 8;6(4):e70097.
doi: 10.1002/jha2.70097. eCollection 2025 Aug.

T-Cell Receptor Repertoires Show Dynamic Variation Between Diagnosis and Relapse of Diffuse Large B-Cell Lymphoma

Joel Wight  1   2   3   4 , Tom Witkowski  2 , Colm Keane  5   6 , Eliza A Hawkes  1   2   3   7
Affiliations

T-Cell Receptor Repertoires Show Dynamic Variation Between Diagnosis and Relapse of Diffuse Large B-Cell Lymphoma

Joel Wight et al. EJHaem. .

Abstract

Background: Tumour infiltrating lymphocyte (TIL) T-cell receptor (TCR) repertoire is prognostic in newly diagnosed diffuse large B-cell lymphoma (DLBCL), but evolution has not been evaluated at relapse.

Methods: We examined the TCR repertoire in nine paired DLBCL samples from diagnosis and relapse.

Results: We noted considerable differences, with dominant clones at diagnosis replaced at relapse by new clones that were absent or minor initially. There was low linearity between diagnostic and relapsed samples (r-values 0.01-0.316), with shared clones averaging 8.3% (range 0%-37%). Clonal diversity was reduced in relapsed samples, suggesting an increasingly defunct intratumoural immune response.

Conclusion: T-cell diversity is reduced in relapsed/refractory DLBCL, which may have implications for immunotherapy usage.

Keywords: DLBCL; T‐cell receptor; diffuse large B cell lymphoma; microenvironment.

PubMed Disclaimer

Conflict of interest statement

Joel Wight has received honoraria from Johnson & Johnson, AbbVie, Sobi, BeiGene, AstraZeneca and MDI, educational subsidies and consulting fees from AbbVie, and has served on the advisory board for Alexion, Johnson & Johnson, and Roche. Colm Keane is on advisory boards for Karyopharm, Roche, Beigene and BMS and has received research funding from Beigene and MSD. Eliza A. Hawkes: Research funding to institution: Bristol Myers Squibb/Celgene, Merck KgaA, AstraZeneca, and F. Hoffmann‐La Roche. Advisory board: F. Hoffmann‐La Roche,* Antigene,* Bristol Myers Squibb, AstraZeneca, Novartis,* Merck Sharpe Dohme,* and Gilead* (*paid to institution). Speaker engagement: Roche (institution), Astra Zeneca (institution), Janssen, and Regeneron. Consultancy: Specialised therapeutics. Tom Witkowski declares no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
T‐cell clones from diagnosis to relapse. (A) Mean CumFreq10 between diagnostic and relapsed samples. (B) Mean CumFreq25 between diagnostic and relapsed samples. (C) Mean CumFreq100 between diagnostic and relapsed samples. (D) The mean percentages of the top four clones in both diagnostic and relapsed samples. Dominant clones at diagnosis are shown in blue/solid lines, and at relapse in yellow/dashed lines. Invariably the trend of the original clones reduced in dominance (or in some cases disappeared entirely), demonstrating that original T‐cell clones tended to be replaced by other T‐cells clones at relapse.
See this image and copyright information in PMC

References

    1. Wight J. C., Chong G., Grigg A. P., and Hawkes E. A., “Prognostication of Diffuse Large B‐Cell Lymphoma in the Molecular Era: Moving Beyond the IPI,” Blood Reviews 32, no. 5 (2018): 400–415. - PubMed
    1. Keane C., Gould C., Jones K., et al., “The T‐Cell Receptor Repertoire Influences the Tumor Microenvironment and Is Associated With Survival in Aggressive B‐Cell Lymphoma,” Clinical Cancer Research 23, no. 7 (2017): 1820–1828. - PubMed
    1. Shanavas M., Law S. C., Hertzberg M., et al., “Intratumoral T‐Cell Receptor Repertoire Is Predictive of Interim PET Scan Results in Patients With Diffuse Large B‐Cell Lymphoma Treated With Rituximab/Cyclophosphamide/Doxorubicin/Prednisolone/Vincristine (R‐CHOP) Chemoimmunotherapy,” Clinical & Translational Immunology 10, no. 11 (2021): e1351. - PMC - PubMed
    1. Charles J., Mouret S., Challende I., et al., “T‐Cell Receptor Diversity as a Prognostic Biomarker in Melanoma Patients,” Pigment Cell & Melanoma Research 33, no. 4 (2020): 612–624. - PubMed
    1. Rudqvist N. P., Pilones K. A., Lhuillier C., et al., “Radiotherapy and CTLA‐4 Blockade Shape the TCR Repertoire of Tumor‐Infiltrating T Cells,” Cancer Immunology Research 6, no. 2 (2018): 139–150. - PMC - PubMed

LinkOut - more resources