Breast cancer associated CD169+ macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells

Gunnarsdottir, Frida Björk; Briem, Oscar; Lindgren, Aida Yifter; Källberg, Eva; Andersen, Cajsa; Grenthe, Robert; Rosenqvist, Cassandra; Millrud, Camilla Rydberg; Wallgren, Mika; Viklund, Hannah; Bexell, Daniel; Johansson, Martin E.; Hedenfalk, Ingrid; Hagerling, Catharina; Leandersson, Karin

doi:10.3389/fimmu.2023.1180209

Cited by 8 publications

(1 citation statement)

References 70 publications

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“…A recent study revealed that CD169+TAMs colocalize with T cells (along with regulatory T cells) in human breast tumors, and suppress T cells and NK cells, possibly via the release of PGE2, ROS and IL-1. 40 It is not known whether CD169+PV TAMs do so in ADT-treated tumors and whether this contributes to the resistance of primary tumors to ADT. Interestingly, a recent study showed that CD169+macrophages promote resistance to the anti-androgen, enzalutamide (an AR antagonist) in mouse (prostate) bone metastases.…”

Section: Discussionmentioning

confidence: 99%

Targeting a STING agonist to perivascular macrophages in prostate tumors delays resistance to androgen deprivation therapy

Al-janabi,

Moyes,

Allen

et al. 2024

J Immunother Cancer

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BackgroundAndrogen deprivation therapy (ADT) is a front-line treatment for prostate cancer. In some men, their tumors can become refractory leading to the development of castration-resistant prostate cancer (CRPC). This causes tumors to regrow and metastasize, despite ongoing treatment, and impacts negatively on patient survival. ADT is known to stimulate the accumulation of immunosuppressive cells like protumoral tumor-associated macrophages (TAMs), myeloid-derived suppressor cells and regulatory T cells in prostate tumors, as well as hypofunctional T cells. Protumoral TAMs have been shown to accumulate around tumor blood vessels during chemotherapy and radiotherapy in other forms of cancer, where they drive tumor relapse. Our aim was to see whether such perivascular (PV) TAMs also accumulate in ADT-treated prostate tumors prior to CRPC, and, if so, whether selectively inducing them to express a potent immunostimulant, interferon beta (IFNβ), would stimulate antitumor immunity and delay CRPC.MethodsWe used multiplex immunofluorescence to assess the effects of ADT on the distribution and activation status of TAMs, CD8+T cells, CD4+T cells and NK cells in mouse and/or human prostate tumors. We then used antibody-coated, lipid nanoparticles (LNPs) to selectively target a STING agonist, 2′3′-cGAMP (cGAMP), to PV TAMs in mouse prostate tumors during ADT.ResultsTAMs accumulated at high density around blood vessels in response to ADT and expressed markers of a protumoral phenotype including folate receptor-beta (FR-β), MRC1 (CD206), CD169 and VISTA. Additionally, higher numbers of inactive (PD-1-) CD8+T cells and reduced numbers of active (CD69+) NK cells were present in these PV tumor areas. LNPs coated with an antibody to FR-β selectively delivered cGAMP to PV TAMs in ADT-treated tumors, where they activated STING and upregulated the expression of IFNβ. This resulted in a marked increase in the density of active CD8+T cells (along with CD4+T cells and NK cells) in PV tumor areas, and significantly delayed the onset of CRPC. Antibody depletion of CD8+T cells during LNP administration demonstrated the essential role of these cells in delay in CRPC induced by LNPs.ConclusionTogether, our data indicate that targeting a STING agonist to PV TAMs could be used to extend the treatment window for ADT in prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Targeting a STING agonist to perivascular macrophages in prostate tumors delays resistance to androgen deprivation therapy

Al-janabi,

Moyes,

Allen

et al. 2024

J Immunother Cancer

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Breast Cancer Immune Landscape: Interplay Between Systemic and Local Immunity

Gerashchenko,

Frolova,

Patysheva

et al. 2024

Advanced Biology

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Breast cancer (BC) is one of the most common malignancies in women worldwide. Numerous studies in immuno‐oncology and successful trials of immunotherapy have demonstrated the causal role of the immune system in cancer pathogenesis. The interaction between the tumor and the immune system is known to have a dual nature. Despite cytotoxic lymphocyte activity against transformed cells, a tumor can escape immune surveillance and leverage chronic inflammation to maintain its own development. Research on antitumor immunity primarily focuses on the role of the tumor microenvironment, whereas the systemic immune response beyond the tumor site is described less thoroughly. Here, a comprehensive review of the formation of the immune profile in breast cancer patients is offered. The interplay between systemic and local immune reactions as self‐sustaining mechanism of tumor progression is described and the functional activity of the main cell populations related to innate and adaptive immunity is discussed. Additionally, the interaction between different functional levels of the immune system and their contribution to the development of the pro‐ or anti‐tumor immune response in BC is highlighted. The presented data can potentially inform the development of new immunotherapy strategies in the treatment of patients with BC.

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Tissue‐Resident Macrophages in Cancer: Friend or Foe?

Chi,

Gao,

Liu

2024

Cancer Medicine

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IntroductionMacrophages are essential in maintaining homeostasis, combating infections, and influencing the process of various diseases, including cancer. Macrophages originate from diverse lineages: Notably, tissue‐resident macrophages (TRMs) differ from hematopoietic stem cells and circulating monocyte‐derived macrophages based on genetics, development, and function. Therefore, understanding the recruited and TRM populations is crucial for investigating disease processes.MethodsBy searching literature databses, we summarized recent relevant studies. Research has shown that tumor‐associated macrophages (TAMs) of distinct origins accumulate in tumor microenvironment (TME), with TRM‐derived TAMs closely resembling gene signatures of normal TRMs.ResultsRecent studies have revealed that TRMs play a crucial role in cancer progression. However, organ‐specific effects complicate TRM investigations. Nonetheless, the precise involvement of TRMs in tumors is unclear. This review explores the multifaceted roles of TRMs in cancer, presenting insights into their origins, proliferation, the latest research methodologies, their impact across various tumor sites, their potential and strategies as therapeutic targets, interactions with other cells within the TME, and the internal heterogeneity of TRMs.ConclusionsWe believe that a comprehensive understanding of the multifaceted roles of TRMs will pave the way for targeted TRM therapies in the treatment of cancer.

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Breast cancer associated CD169+ macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells

Cited by 8 publications

References 70 publications

Targeting a STING agonist to perivascular macrophages in prostate tumors delays resistance to androgen deprivation therapy

Targeting a STING agonist to perivascular macrophages in prostate tumors delays resistance to androgen deprivation therapy

Breast Cancer Immune Landscape: Interplay Between Systemic and Local Immunity

Tissue‐Resident Macrophages in Cancer: Friend or Foe?

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