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Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer

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.
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https://www.hal.inserm.fr/inserm-03653110
Contributor : Pierre Laurent-Puig Connect in order to contact the contributor
Submitted on : Wednesday, April 27, 2022 - 1:11:19 PM
Last modification on : Thursday, May 5, 2022 - 3:11:43 AM

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Maxime Meylan, Florent Petitprez, Etienne Becht, Antoine Bougoüin, Guilhem Pupier, et al.. Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer. Immunity, Elsevier, 2022, 55 (3), pp.527-541.e5. ⟨10.1016/j.immuni.2022.02.001⟩. ⟨inserm-03653110⟩

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