Skip to nav Skip to content
Brian  Ruffell

Brian Ruffell, PhD

Program: Immunology

Research Program: Immuno-Oncology Program

View Lab Page

Google Scholar Profile


  • Overview


    • Immunology
    • Breast Oncology
    • Immuno-Oncology Program
    • Lung Cancer Center of Excellence

    Education & Training


    • University of British Columbia, PhD - Molecular Immunology


    • University of California, San Francisco - Cancer Immunology
    • Oregon Health & Science University - Cancer Immunology
  • Research Interest

    Effectively harnessing the power of the immune system is one of the most promising advances in cancer therapy. Immune-based therapies take advantage of the tumor killing capacity of cytotoxic T cells, an ability that is normally limited within tumors via multiple suppressive pathways. Supporting the activity of these cytotoxic T cells can provide long-term survival advantages, but despite recent successes, only a fraction of patients respond to immunotherapy, and efficacious treatment has so far been largely limited to select tumor types. The identification of additional therapeutic targets is urgently needed to address these issues and expand upon the number of patients who will benefit from this relatively safe and effective treatment approach. The Ruffell Lab is focused on understanding the role of key myeloid subsets within hormone-drive malignancies in order to identify and develop novel therapeutic targets and approaches.

  • Publications

    • Hänggi K, Ruffell B. Cell death, therapeutics, and the immune response in cancer. Trends Cancer. 2023 May.9(5):381-396. Pubmedid: 36841748. Pmcid: PMC10121860.
    • Lockhart JH, Ackerman HD, Lee K, Abdalah M, Davis AJ, Hackel N, Boyle TA, Saller J, Keske A, Hänggi K, Ruffell B, Stringfield O, Cress WD, Tan AC, Flores ER. Grading of lung adenocarcinomas with simultaneous segmentation by artificial intelligence (GLASS-AI). NPJ Precis Oncol. 2023 Jul.7(1):68. Pubmedid: 37464050. Pmcid: PMC10354042.
    • Lester DK, Burton C, Gardner A, Innamarato P, Kodumudi K, Liu Q, Adhikari E, Ming Q, Williamson DB, Frederick DT, Sharova T, White MG, Markowitz J, Cao B, Nguyen J, Johnson J, Beatty M, Mockabee-Macias A, Mercurio M, Watson G, Chen PL, McCarthy S, MoranSegura C, Messina J, Thomas KL, Darville L, Izumi V, Koomen JM, Pilon-Thomas SA, Ruffell B, Luca VC, Haltiwanger RS, Wang X, Wargo JA, Boland GM, Lau EK. Fucosylation of HLA-DRB1 regulates CD4+ T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy. Nat Cancer. 2023 Feb.4(2):222-239. Pubmedid: 36690875. Pmcid: PMC9970875.
    • Zheng H, Yu X, Ibrahim ML, Foresman D, Xie M, Johnson JO, Boyle TA, Ruffell B, Perez BA, Antonia SJ, Ready N, Saltos AN, Cantwell MJ, Beg AA. Combination IFNβ and Membrane-Stable CD40L Maximize Tumor Dendritic Cell Activation and Lymph Node Trafficking to Elicit Systemic T-cell Immunity. Cancer Immunol Res. 2023 Apr.11(4):466-485. Pubmedid: 36757308. Pmcid: PMC10165690.
    • Celias DP, de Mingo Pulido Á, Ruffell B. Detection of exogenous DNA uptake by murine dendritic cells. STAR Protoc. 2022 Sep.3(3):101464. Pubmedid: 35719726. Pmcid: PMC9204794.
    • Li J, Ruffell B. Cytokines drive prostate cancer lineage plasticity. Immunity. 2022 Oct.55(10):1761-1763. Pubmedid: 36223725.
    • Mandula JK, Chang S, Mohamed E, Jimenez R, Sierra-Mondragon RA, Chang DC, Obermayer AN, Moran-Segura CM, Das S, Vazquez-Martinez JA, Prieto K, Chen A, Smalley KSM, Czerniecki B, Forsyth P, Koya RC, Ruffell B, Cubillos-Ruiz JR, Munn DH, Shaw TI, Conejo-Garcia JR, Rodriguez PC. Ablation of the endoplasmic reticulum stress kinase PERK induces paraptosis and type I interferon to promote anti-tumor T cell responses. Cancer Cell. 2022 Oct.40(10):1145-1160.e9. Pubmedid: 36150390. Pmcid: PMC9561067.
    • Ming Q, Celias DP, Wu C, Cole AR, Singh S, Mason C, Dong S, Tran TH, Amarasinghe GK, Ruffell B, Luca VC. LAG3 ectodomain structure reveals functional interfaces for ligand and antibody recognition. Nat Immunol. 2022 Jul.23(7):1031-1041. Pubmedid: 35761082. Pmcid: PMC10191176.
    • Gardner A, de Mingo Pulido Á, Hänggi K, Bazargan S, Onimus A, Kasprzak A, Conejo-Garcia JR, Rejniak KA, Ruffell B. TIM-3 blockade enhances IL-12-dependent antitumor immunity by promoting CD8+ T cell and XCR1+ dendritic cell spatial co-localization. J Immunother Cancer. 2022 Jan.10(1). Pubmedid: 34987021. Pmcid: PMC8734033.
    • Li J, DeNicola GM, Ruffell B. Metabolism in tumor-associated macrophages. Int Rev Cell Mol Biol. 2022 Apr.367:65-100. Pubmedid: 35461660. Pmcid: PMC9094395.
    • El-Kenawi A, Dominguez-Viqueira W, Liu M, Awasthi S, Abraham-Miranda J, Keske A, Steiner KK, Noel L, Serna AN, Dhillon J, Gillies RJ, Yu X, Koomen JM, Yamoah K, Gatenby RA, Ruffell B. Macrophage-Derived Cholesterol Contributes to Therapeutic Resistance in Prostate Cancer. Cancer Res. 2021 Nov.81(21):5477-5490. Pubmedid: 34301759. Pmcid: PMC8563406.
    • de Mingo Pulido Á, Hänggi K, Celias DP, Gardner A, Li J, Batista-Bittencourt B, Mohamed E, Trillo-Tinoco J, Osunmakinde O, Peña R, Onimus A, Kaisho T, Kaufmann J, McEachern K, Soliman H, Luca VC, Rodriguez PC, Yu X, Ruffell B. The inhibitory receptor TIM-3 limits activation of the cGAS-STING pathway in intra-tumoral dendritic cells by suppressing extracellular DNA uptake. Immunity. 2021 Jun.54(6):1154-1167.e7. Pubmedid: 33979578. Pmcid: PMC8192496.
    • Rodriguez PC, Ruffell B. Cavity macrophages stop anti-tumor T cells. Cancer Cell. 2021 Jul.39(7):900-902. Pubmedid: 34256904.
    • Gardner A, de Mingo Pulido Á, Ruffell B. Dendritic Cells and Their Role in Immunotherapy. Front Immunol. 2020 May.11:924. Pubmedid: 32508825. Pmcid: PMC7253577.
    • El-Kenawi A, Gatenbee C, Robertson-Tessi M, Bravo R, Dhillon J, Balagurunathan Y, Berglund A, Vishvakarma N, Ibrahim-Hashim A, Choi J, Luddy K, Gatenby R, Pilon-Thomas S, Anderson A, Ruffell B, Gillies R. Correction: Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer. Brit J Cancer. 2020 Mar.122(7):1118. Pubmedid: 31937927. Pmcid: PMC7109119.
    • Mohamed E, Sierra RA, Trillo-Tinoco J, Cao Y, Innamarato P, Payne KK, de Mingo Pulido A, Mandula J, Zhang S, Thevenot P, Biswas S, Abdalla SK, Costich TL, Hänggi K, Anadon CM, Flores ER, Haura EB, Mehrotra S, Pilon-Thomas S, Ruffell B, Munn DH, Cubillos-Ruiz JR, Conejo-Garcia JR, Rodriguez PC. The Unfolded Protein Response Mediator PERK Governs Myeloid Cell-Driven Immunosuppression in Tumors through Inhibition of STING Signaling. Immunity. 2020 Apr.52(4):668-682.e7. Pubmedid: 32294407. Pmcid: PMC7207019.
    • El-Kenawi A, Hänggi K, Ruffell B. The Immune Microenvironment and Cancer Metastasis. Cold Spring Harb Perspect Med. 2020 Apr.10(4). Pubmedid: 31501262. Pmcid: PMC7117953.
    • El-Kenawi A, Gatenbee C, Robertson-Tessi M, Bravo R, Dhillon J, Balagurunathan Y, Berglund A, Visvakarma N, Ibrahim-Hashim A, Choi J, Luddy K, Gatenby R, Pilon-Thomas S, Anderson A, Ruffell B, Gillies R. Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer. Brit J Cancer. 2019 Oct.121(7):556-566. Pubmedid: 31417189. Pmcid: PMC6889319.
    • Trillo-Tinoco J, Sierra RA, Mohamed E, Cao Y, de Mingo-Pulido Á, Gilvary DL, Anadon CM, Costich TL, Wei S, Flores ER, Ruffell B, Conejo-Garcia JR, Rodriguez PC. AMPK Alpha-1 Intrinsically Regulates the Function and Differentiation of Tumor Myeloid-Derived Suppressor Cells. Cancer Res. 2019 Oct.79(19):5034-5047. Pubmedid: 31409640. Pmcid: PMC6774829.
    • DeNardo DG, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol. 2019 Jun.19(6):369-382. Pubmedid: 30718830. Pmcid: PMC7339861.
    • Hänggi K, Ruffell B. Oncogenic KRAS Drives Immune Suppression in Colorectal Cancer. Cancer Cell. 2019 Apr.35(4):535-537. Pubmedid: 30991021.
    • Reddy JP, Atkinson RL, Larson R, Burks JK, Smith D, Debeb BG, Ruffell B, Creighton CJ, Bambhroliya A, Reuben JM, Van Laere SJ, Krishnamurthy S, Symmans WF, Brewster AM, Woodward WA. Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer. Breast Cancer Res Treat. 2018 Sep.171(2):283-293. Pubmedid: 29858753.
    • Betts CB, Pennock ND, Caruso BP, Ruffell B, Borges VF, Schedin P. Mucosal Immunity in the Female Murine Mammary Gland. J Immunol. 2018 Jul.201(2):734-746. Pubmedid: 29884705. Pmcid: PMC6036228.
    • de Mingo Pulido Á, Gardner A, Hiebler S, Soliman H, Rugo HS, Krummel MF, Coussens LM, Ruffell B. TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer. Cancer Cell. 2018 Jan.33(1):60-74.e6. Pubmedid: 29316433. Pmcid: PMC5764109.
    • Gardner A, Ruffell B. moDCs, Less Problems. Immunity. 2018 01.48(1):6-8. Pubmedid: 29343441.
    • Gardner A, Ruffell B. Reducing interferon'ce in stem cells. Nat Cell Biol. 2017 May.19(6):597-599. Pubmedid: 28561058.
    • de Mingo Pulido A, Ruffell B. Immune Regulation of the Metastatic Process: Implications for Therapy. Adv Cancer Res. 2017 Jun.132:139-163. Pubmedid: 27613132. Pmcid: PMC5364524.
    • Bergstrom CP, Ruffell B, Ho CM, Higano CS, Ellis WJ, Garzotto M, Beer TM, Graff JN. Docetaxel and mitoxantrone before radical prostatectomy in men with high-risk prostate cancer: 10-year follow-up and immune correlates. Anticancer Drugs. 2017 Jan.28(1):120-126. Pubmedid: 27669423. Pmcid: PMC7370800.
    • El-Kenawi A, Ruffell B. Inflammation, ROS, and Mutagenesis. Cancer Cell. 2017 Dec.32(6):727-729. Pubmedid: 29232551.
    • Gunderson AJ, Kaneda MM, Tsujikawa T, Nguyen AV, Affara NI, Ruffell B, Gorjestani S, Liudahl SM, Truitt M, Olson P, Kim G, Hanahan D, Tempero MA, Sheppard B, Irving B, Chang BY, Varner JA, Coussens LM. Bruton Tyrosine Kinase-Dependent Immune Cell Cross-talk Drives Pancreas Cancer. Cancer Discov. 2016 Mar.6(3):270-285. Pubmedid: 26715645. Pmcid: PMC4783268.
    • Wolfe AR, Trenton NJ, Debeb BG, Larson R, Ruffell B, Chu K, Hittelman W, Diehl M, Reuben JM, Ueno NT, Woodward WA. Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models. Oncotarget. 2016 Dec.7(50):82482-82492. Pubmedid: 27756885. Pmcid: PMC5347707.
    • Gardner A, Ruffell B. Dendritic Cells and Cancer Immunity. Trends Immunol. 2016 Dec.37(12):855-865. Pubmedid: 27793569. Pmcid: PMC5135568.
    • Zheng H, Zhao W, Yan C, Watson CC, Messengill M, Xie M, Messengill C, Noyes D, Martinez GV, Afzal R, Chen Z, Ren X, Antonia SJ, Haura EB, Ruffell B, Beg AA. HDAC Inhibitors Enhance T-Cell Chemokine Expression and Augment Response to PD-1 Immunotherapy in Lung Adenocarcinoma. Clin Cancer Res. 2016 Aug.22(16):4119-4132. Pubmedid: 26964571. Pmcid: PMC4987196.
    • Juric V, Ruffell B, Evason KJ, Hu J, Che L, Wang L, Chen X, Bishop JM. Monocytes promote liver carcinogenesis in an oncogene-specific manner. J Hepatol. 2016 Apr.64(4):881-890. Pubmedid: 26639397. Pmcid: PMC4799762.
    • Pilon-Thomas S, Ruffell B. Tipping the Balancing ACT. Cancer Cell. 2016 09.30(3):367-368. Pubmedid: 27622327.
    • Shiao SL, Ruffell B, DeNardo DG, Faddegon BA, Park CC, Coussens LM. TH2-Polarized CD4(+) T Cells and Macrophages Limit Efficacy of Radiotherapy. Cancer Immunol Res. 2015 May.3(5):518-525. Pubmedid: 25716473. Pmcid: PMC4420686.
    • Wolfe AR, Debeb BG, Lacerda L, Larson R, Bambhroliya A, Huang X, Bertucci F, Finetti P, Birnbaum D, Van Laere S, Diagaradjan P, Ruffell B, Trenton NJ, Chu K, Hittelman W, Diehl M, Levental I, Ueno NT, Woodward WA. Simvastatin prevents triple-negative breast cancer metastasis in pre-clinical models through regulation of FOXO3a. Breast Cancer Res Treat. 2015 Dec.154(3):495-508. Pubmedid: 26590814. Pmcid: PMC5901982.
    • Ruffell B, Coussens LM. Macrophages and therapeutic resistance in cancer. Cancer Cell. 2015 Apr.27(4):462-472. Pubmedid: 25858805. Pmcid: PMC4400235.
    • Ruffell B, Chang-Strachan D, Chan V, Rosenbusch A, Ho CM, Pryer N, Daniel D, Hwang ES, Rugo HS, Coussens LM. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell. 2014 Nov.26(5):623-637. Pubmedid: 25446896. Pmcid: PMC4254570.
    • Affara NI, Ruffell B, Medler TR, Gunderson AJ, Johansson M, Bornstein S, Bergsland E, Steinhoff M, Li Y, Gong Q, Ma Y, Wiesen JF, Wong MH, Kulesz-Martin M, Irving B, Coussens LM. B cells regulate macrophage phenotype and response to chemotherapy in squamous carcinomas. Cancer Cell. 2014 Jun.25(6):809-821. Pubmedid: 24909985. Pmcid: PMC4063283.
    • Ruffell B, Affara NI, Cottone L, Junankar S, Johansson M, DeNardo DG, Korets L, Reinheckel T, Sloane BF, Bogyo M, Coussens LM. Cathepsin C is a tissue-specific regulator of squamous carcinogenesis. Gene Dev. 2013 Oct.27(19):2086-2098. Pubmedid: 24065739. Pmcid: PMC3850093.
    • Strachan DC, Ruffell B, Oei Y, Bissell MJ, Coussens LM, Pryer N, Daniel D. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+ T cells. Oncoimmunology. 2013 Dec.2(12):e26968. Pubmedid: 24498562. Pmcid: PMC3902121.
    • Ganesan AP, Johansson M, Ruffell B, Yagui-Beltrán A, Beltran A, Lau J, Jablons DM, Coussens LM. Tumor-infiltrating regulatory T cells inhibit endogenous cytotoxic T cell responses to lung adenocarcinoma. J Immunol. 2013 Aug.191(4):2009-2017. Pubmedid: 23851682. Pmcid: PMC3774528.
    • Ruffell B, Coussens LM. Some DCs are "B"etter. Immunity. 2013 Apr.38(4):626-628. Pubmedid: 23601679.
    • Ruffell B, Affara NI, Coussens LM. Differential macrophage programming in the tumor microenvironment. Trends Immunol. 2012 Mar.33(3):119-126. Pubmedid: 22277903. Pmcid: PMC3294003.
    • Ruffell B, Au A, Rugo HS, Esserman LJ, Hwang ES, Coussens LM. Leukocyte composition of human breast cancer. Proc Natl Acad Sci U S A. 2012 Feb.109(8):2796-2801. Pubmedid: 21825174. Pmcid: PMC3287000.
    • Daldrup-Link HE, Golovko D, Ruffell B, Denardo DG, Castaneda R, Ansari C, Rao J, Tikhomirov GA, Wendland MF, Corot C, Coussens LM. MRI of tumor-associated macrophages with clinically applicable iron oxide nanoparticles. Clin Cancer Res. 2011 Sep.17(17):5695-5704. Pubmedid: 21791632. Pmcid: PMC3166957.
    • DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, Gallagher WM, Wadhwani N, Keil SD, Junaid SA, Rugo HS, Hwang ES, Jirström K, West BL, Coussens LM. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 2011 Jun.1(1):54-67. Pubmedid: 22039576. Pmcid: PMC3203524.
    • Ruffell B, Poon GF, Lee SS, Brown KL, Tjew SL, Cooper J, Johnson P. Differential use of chondroitin sulfate to regulate hyaluronan binding by receptor CD44 in Inflammatory and Interleukin 4-activated Macrophages. J Biol Chem. 2011 Jun.286(22):19179-19190. Pubmedid: 21471214. Pmcid: PMC3103297.
    • Ruffell B, Coussens LM. Histamine restricts cancer: nothing to sneeze at. Nat Med. 2011 Jan.17(1):43-44. Pubmedid: 21217680.
    • Ruffell B, DeNardo DG, Affara NI, Coussens LM. Lymphocytes in cancer development: polarization towards pro-tumor immunity. Cytokine Growth Factor Rev. 2010 Feb.21(1):3-10. Pubmedid: 20005150. Pmcid: PMC2834837.
    • Johnson P, Ruffell B. CD44 and its role in inflammation and inflammatory diseases. Inflamm Allergy Drug Targets. 2009 Jul.8(3):208-220. Pubmedid: 19601881.
    • Ruffell B, Johnson P. Hyaluronan induces cell death in activated T cells through CD44. J Immunol. 2008 Nov.181(10):7044-7054. Pubmedid: 18981124.
    • Ruffell B, Johnson P. Chondroitin sulfate addition to CD44H negatively regulates hyaluronan binding. Biochem Bioph Res Co. 2005 Aug.334(2):306-312. Pubmedid: 16002044.
    • Khan AI, Kerfoot SM, Heit B, Liu L, Andonegui G, Ruffell B, Johnson P, Kubes P. Role of CD44 and hyaluronan in neutrophil recruitment. J Immunol. 2004 Dec.173(12):7594-7601. Pubmedid: 15585887.
  • Grants

    • Title: Targeting ENPP1 to promote immunity during PARP inhibition in TNBC
      Sponsor: US Army
      PI (Contact): Ruffell, B.
    • Title: Targeting dendritic cells to improve cancer immunotherapy
      Sponsor: Cancer Research Institute
      PI: Ruffell, B.
    • Title: Regulation of dendritic cell function and tumor immunity by TIM-3
      Sponsor: Nat Institutes of Health
      PI: Ruffell, B.

Find a Researcher Search