Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer
Open accessAbstract
The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS, and the presence of fully mature clonotypes at distance. In TLS+ tumors, IgG- and IgA-producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptotic malignant cells, suggestive of anti-tumor effector activity. Therapeutic responses and progression-free survival correlated with IgG-stained tumor cells in RCC patients treated with immune checkpoint inhibitors. Thus, intratumoral TLS sustains B cell maturation and antibody production that is associated with response to immunotherapy, potentially via direct anti-tumor effects.
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Tumor-associated tertiary lymphoid structures are emerging as a powerful prognostic marker in melanoma and a number of other cancer types.
“Also, as a member of the 12-chemokine gene signature classifier33, its expression has been correlated with the presence of tumor-associated tertiary lymphoid structures50–52 which are rapidly emerging as a powerful prognostic marker in melanoma and a number of other cancer types53–55.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [55]
In RCC patients receiving ICIs, tertiary lymphoid structures favoured in situ B cell maturation and differentiation into IgG-secreting plasma cells.
“Analysis of tumour tissue from three cohorts of patients who had received ICIs revealed that, in those harbouring tertiary lymphoid structures (TLS), these structures favoured in situ B cell maturation and differentiation into IgG-secreting plasma cells.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [119]
RCC patients with TLS+ tumours and IgG-labelled tumour cells had higher ORR and longer PFS than those with TLS+ tumours without IgG labelling.
“Patients with TLS+ tumours and IgG-labelled RCC cells had higher ORR and prolonged PFS than those with TLS+ tumours and no IgG labelling119.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [119]
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- Authors
- Meylan, M., Petitprez, F., Becht, E., Bougoüin, A., Pupier, G., Calvez, A., Giglioli, I., Verkarre, V., Lacroix, G., Verneau, J., Sun, C.-M., Laurent-Puig, P., Vano, Y.-A., Elaïdi, R., Méjean, A., Sanchez-Salas, R., Barret, E., Cathelineau, X., Oudard, S., Reynaud, C.-A., de Reyniès, A., Sautès-Fridman, C., & Fridman, W. H.
- Affiliations
- Inserm (FR)
- La Ligue Contre le Cancer (FR)
- Université Paris Cité (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Fridman, Wolf Herman
- ORCID
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- Immunity
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- Elsevier BV
- Published
- 2022-03
- Volume
- 55
- Issue
- 3
- Pages
- 527-541.e5
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W4214620261
- Cited by
- 831
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- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-10-LABX-0015)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- tertiary lymphoid structures, renal cell carcinoma, plasma cells, B cell maturation, anti-tumor antibodies, IgG, IgA, B cell receptor repertoire, clonal diversification, immune checkpoint inhibitors, spatial transcriptomics, tumor microenvironment
- MeSH terms
- Tertiary Lymphoid Structures, Carcinoma, Renal Cell, Female, Humans, Immunoglobulin G, Kidney Neoplasms, Male, Plasma Cells, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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