Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer.
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IF: 43.474
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Cited by: 142
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Datasets
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Abstract

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.

Keywords

Spatial Transcriptomics
B cell maturation
B cell repertoire
Visium
anti-tumor IgG
fibroblasts
plasma cells
renal cell cancer
response to immune check point inhibition
spatial transcriptomics
tertiary lymphoid structures
tumor microenvironment

Authors

Meylan, Maxime
Petitprez, Florent
Becht, Etienne
Bougoüin, Antoine
Pupier, Guilhem
Calvez, Anne
Giglioli, Ilenia
Verkarre, Virginie
Lacroix, Guillaume
Verneau, Johanna
Sun, Chen-Ming
Laurent-Puig, Pierre
Vano, Yann-Alexandre
Elaïdi, Reza
Méjean, Arnaud
Sanchez-Salas, Rafaël
Barret, Eric
Cathelineau, Xavier
Oudard, Stephane
Reynaud, Claude-Agnès
de Reyniès, Aurélien
Sautès-Fridman, Catherine
Fridman, Wolf Herman

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