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The first thing a lymphoma report says is which kind of lymphocyte the cancer came from. B cells make antibodies and carry a surface protein called CD20; T and NK cells kill infected cells directly and carry no CD20. That single difference is why B-cell lymphomas have had thirty years of new antibody treatments and T-cell lymphomas have not.
Lymphocytes come in three lineages and a lymphoma inherits the one it arose from. B cells mature in the bone marrow and in the germinal centres of lymph nodes, and make antibodies. T cells mature in the thymus and either help other immune cells or kill infected ones. Natural killer cells kill without needing to recognise a specific antigen, and share many surface proteins with cytotoxic T cells, which is why the classifications treat T-cell and NK-cell lymphomas as one group.
The proportions are lopsided. In the UK Haematological Malignancy Research Network series of 5,796 lymphomas, 94.7 per cent were B-cell and 5.3 per cent T-cell. The outcomes are lopsided in the same direction: five-year relative survival was 68.8 per cent for the B-cell group and 45.4 per cent for the T-cell group.
The reason is mostly pharmacological rather than biological. B cells carry CD20, a protein with no essential function that the body can do without, so an antibody against it can be given safely and kills the lymphoma along with the normal B cells. Rituximab was licensed in 1997 and every later B-cell treatment, from antibody-drug conjugates to CAR-T to bispecific antibodies, built on the same idea of a surface address. T cells have no equivalent: the obvious targets are proteins the healthy T cells need, so removing them removes the immune system, and a CAR-T cell aimed at a T-cell protein attacks the other CAR-T cells, a problem called fratricide that the engineering is only now starting to solve.
On a report, the lineage is read from immunohistochemistry: CD20, CD79a and PAX5 for B cells, CD3, CD2, CD5 and CD7 for T cells, CD56 and cytoplasmic CD3 for NK cells. A clonal rearrangement of the immunoglobulin or T-cell receptor genes confirms that the population is a single clone rather than a reaction.
Backbone ribbon from PDB 6VJA. RCSB PDB 6VJA. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
Showing the molecule this term concerns: Rituximab.
Shares ALK-negative anaplastic large cell lymphoma, ALK-positive anaplastic large cell lymphoma, Adult T-cell leukaemia/lymphoma, Extranodal NK/T-cell lymphoma and the tags heme, lymphoma.
Shares T-cell/histiocyte-rich large B-cell lymphoma, Lymphoma (tissue type), The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC), Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome) and the tags heme, lymphoma.
Shares Adult T-cell leukaemia/lymphoma, Lymphoma (tissue type), Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Non-Hodgkin lymphoma (all types) and the tags heme, lymphoma.
Shares Breast implant-associated anaplastic large cell lymphoma, Plasmablastic lymphoma, Lymphoma (tissue type), Extranodal NK/T-cell lymphoma and the tags heme, lymphoma.
Shares T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC), CD20 and the tags heme, lymphoma.
Shares Diffuse large B-cell lymphoma, Non-Hodgkin lymphoma (all types) and the tags heme, lymphoma.
Shares Non-Hodgkin lymphoma (all types) and the tags heme, lymphoma.
Shares ALK-negative anaplastic large cell lymphoma, ALK-positive anaplastic large cell lymphoma, The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC), Brentuximab vedotin and the tags heme, lymphoma.