Solid tumour-induced systemic immunosuppression involves dichotomous myeloid–B cell interactions

Menée à l'aide de modèles murins, d'échantillons de moelle osseuse d'origine humaine ainsi que d'échantillons sanguins prélevés sur des femmes en bonne santé ou des patientes atteintes d'un cancer du sein triple négatif, cette étude met en évidence deux mécanismes distincts par lequel des tumeurs solides peuvent induire une immunosuppression systémique en favorisant la formation de lymphocytes B anormaux

Résumé en anglais

Solid tumours induce systemic immunosuppression that involves myeloid and T cells. B cell-related mechanisms remain relatively understudied. Here we discover two distinct patterns of tumour-induced B cell abnormality (TiBA; TiBA-1 and TiBA-2), both associated with abnormal myelopoiesis in the bone marrow. TiBA-1 probably results from the niche competition between pre-progenitor-B cells and myeloid progenitors, leading to a global reduction in downstream B cells. TiBA-2 is characterized by systemic accumulation of a unique early B cell population, driven by interaction with excessive neutrophils. Importantly, TiBA-2-associated early B cells foster the systemic accumulation of exhaustion-like T cells. Myeloid and B cells from the peripheral blood of patients with triple-negative breast cancer recapitulate the TiBA subtypes, and the distinct TiBA profile correlates with pathologic complete responses to standard-of-care immunotherapy. This study underscores the inter-patient diversity of tumour-induced systemic changes and emphasizes the need for treatments tailored to different B and myeloid cell abnormalities.