Immunosuppressive plasma cells impede T cell-dependent immunogenic chemotherapy

Cancer-associated genetic alterations induce expression of tumour antigens that can activate CD8+ cytotoxic T cells (CTLs), but the microenvironment of established tumours promotes immune tolerance through poorly understood mechanisms. Recently developed therapeutics that overcome tolerogenic mechanisms activate tumour-directed CTLs and are effective in some human cancers. Immune mechanisms also affect treatment outcome, and certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death and other effector mechanisms. Our previous studies revealed that B cells recruited by the chemokine CXCL13 into prostate cancer tumours promote the progression of castrate-resistant prostate cancer by producing lymphotoxin, which activates an IκB kinase α (IKKα)-BMI1 module in prostate cancer stem cells. Because castrate-resistant prostate cancer is refractory to most therapies, we examined B cell involvement in the acquisition of chemotherapy resistance. Here we focus on oxaliplatin, an immunogenic chemotherapeutic agent that is effective in aggressive prostate cancer. We show that mouse B cells modulate the response to low-dose oxaliplatin, which promotes tumour-directed CTL activation by inducing immunogenic cell death. Three different mouse prostate cancer models were refractory to oxaliplatin unless genetically or pharmacologically depleted of B cells. The crucial immunosuppressive B cells are plasmocytes that express IgA, interleukin (IL)-10 and programmed death ligand 1 (PD-L1), the appearance of which depends on TGFβ receptor signalling. Elimination of these cells, which also infiltrate human-therapy-resistant prostate cancer, allows CTL-dependent eradication of oxaliplatin-treated tumours.

• Publication year

  2015

• Venue

  Nature

• Publication date

  2015-03-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/nature14395PMID 25924065PMCID 4501632
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Biomarkers in cancer immunotherapy.

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• Tolerance and exhaustion: defining mechanisms of T cell dysfunction.

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  2014cited by this paper
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  2014cited by this paper
• Immunogenic cell death in cancer therapy.

  2013cited by this paper
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• An IKKα-E2F1-BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence.

  2013cited by this paper
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  2011cited by this paper
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  2011cited by this paper
• Treg cell-IgA axis in maintenance of host immune homeostasis with microbiota.

  2011cited by this paper
• B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging.

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• B-cell-derived lymphotoxin promotes castration-resistant prostate cancer

  2010cited by this paper
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  2009cited by this paper
• The regulation of IgA class switching

  2008cited by this paper
• Tumor immunobiological differences in prostate cancer between African-American and European-American men.

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  2007cited by this paper
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  2004cited by this paper
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  2002cited by this paper
• Expression profiling reveals hepsin overexpression in prostate cancer.

  2001cited by this paper
• Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer.

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• Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes.

  1999cited by this paper
• Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer.

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• B cells inhibit induction of T cell-dependent tumor immunity

  1998cited by this paper
• Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model.

  1997cited by this paper
• Metastatic prostate cancer in a transgenic mouse.

  1996cited by this paper
• T cell receptor antagonist peptides induce positive selection.

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• Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus.

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