Cancer immunology lab @MoffittResearch investigating the role of dendritic cells and macrophages in breast and prostate cancer.
Joined March 2021
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Thrilled to share our story out in Cancer Cell, led by the amazing Kay Hanggi (now on the job market). We show that necrotic forms of cell death and the subsequent release of IL1a drives myeloid-based immune suppression in models of breast cancer. (1/11)
cell.com/cancer-cell/abstrac…
Ruffell Lab retweeted
Interleukin-1α release during necrotic-like cell death generates myeloid-driven immunosuppression that restricts anti-tumor immunity dlvr.it/TGhVzG
Ruffell Lab retweeted
Excited to share our latest by @Triantafyllia14 where we find that IFNg acts as a metabolic switch to prune tumor-associated lymphangiogenesis and unlink immune surveillance and metastasis biorxiv.org/content/10.1101/… #theLundLab
Ruffell Lab retweeted
#ScienceSaturday
➡️ Did you know that some chemotherapies can enhance the immune response against #cancer?
❓ How might we potentiate this?
➡️ @Ruffell_Lab and colleagues from @moffittnews found that the necrotic cell death induced by #chemotherapy releases IL-1 alpha which induces immunosuppressive myeloid cells. Inhibiting IL-1 alpha in combination with chemotherapy enhanced antitumor responses.
‼️ This may be a promising approach for future clinical trials.
🔗 Here’s a link to the full study- cell.com/cancer-cell/abstrac…
@Cancer_Cell
Thanks to Kay for his dedication to the project and the lab over the years. Also to everyone that contributed, including those on the app: @gatechatl @DeNardoLabWUSM @CeliasDaiana (11/11)
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Finally, it is unclear if there are divergent roles for tumor IL1a versus host IL1B due to different expression patterns or methods of release. (10/11)
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Questions remain regarding the type of necrotic death necessary for IL1a release, especially in the context of therapy, and which immune or strongly populations are responding to IL1a. (9/11)
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IL1R-deficient tumors also displayed enhanced response to chemotherapy, highlighting an interaction between dying tumor cells and their remaining neighbors. (8/11)
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Although myeloid-produced IL1a is critical for lung cancer growth in aged mice (beautifully described by @MatthewD_Park and @MiriamMerad), neutralizing host IL1a had no further impact in our young models of breast cancer. (7/11)
science.org/doi/10.1126/scie…
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We then tested if IL1a-deficient tumors were more sensitive to chemotherapy or chemoimmunotherapy, and found improved responses to both. This included an additional model of TNBC. Treatment efficacy was similarly enhanced by the use of an IL1a neutralizing antibody. (6/11)
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There was also a striking shift towards CXCL9 expression and away from SPP1 expression, which has been shown to correlate with positive outcomes by @PittetLab (5/11)
science.org/doi/10.1126/scie…
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Knocking out Il1a in tumors produced only minimal change in tumor growth, but improved T cell effector function. Critically, macrophages isolated from IL1a-deficient tumors completely lost their suppressive capacity. (4/11)
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In vitro studies showed necroptosis induced chemokine expression by tumor cells (even with MLKL alone), with the supernatant being highly potent when added to live cells. Chemokine expression was MyD88-dependent and was blocked by inhibiting IL1R or IL1a, but not IL1B (3/11)
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The project started with Kay wanting to understand how necroptosis within tumors would promote anti-tumor immunity. However, when using genetic tools to induce necroptosis in PyMT mammary tumors he found they grew faster with reduced T cell effector function. (2/11)
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Ruffell Lab retweeted
People, the IL-1 pathway is SO RELEVANT in cancer 🔥🔥 IL-1a released from dying tumor cells dampens anti-tumor immunity by recruiting immune suppressive myeloid cells - this limits efficacy of chemo and ICB
by Brian Ruffel in @Cancer_Cell
cell.com/cancer-cell/fulltex…
Ruffell Lab retweeted
Online Now: Interleukin-1α release during necrotic-like cell death generates myeloid-driven immunosuppression that restricts anti-tumor immunity dlvr.it/TGJwxg
Ruffell Lab retweeted
Check out our latest paper “Differentiation fate of a stem-like CD4 T cell control immunity to cancer”, led by @Maria_Carden1 now live @Nature tinyurl.com/33d24k89 . This work examines how CD4 T cell differentiation dictates the outcome of the cancer response. Thread below
Ruffell Lab retweeted
Our new study published today @Nature uncovers that Transgelin 2 preserves T cell lipid metabolism and anti-tumor activity. Transgelin 2 is silenced in dysfunctional TILs, and restoring its expression enhances CAR-T cell therapy in #OvarianCancer 👇nature.com/articles/s41586-0…
Ruffell Lab retweeted
Congratulations Dr. Liu @SitemanCenter and collaborators @LabBeatty and K.Bryant on their featured article in @ScienceTM . And HUDGE THANKS to @PanCAN for bringing this team together and funding the trial that came out of the science with @verastemoncology.
Ruffell Lab retweeted
Our review on a topic we eagerly enjoy exploring in the lab- how our fav immune cell types influence/are influenced by metabolic disorders preceding cancer- so much to learn! 👏🏻👏🏻 to #DanielTaranto for leading the effort, to @djkloosterman and the whole lab for their input! 🔥🔥
NEW content online! Macrophages and T cells in metabolic disorder-associated cancers go.nature.com/4duhbCv
