Mark J Smyth



  1. request reprint
    Ngiow S, Young A, Blake S, Hill G, Yagita H, Teng M, et al. Agonistic CD40 mAb-Driven IL12 Reverses Resistance to Anti-PD1 in a T-cell-Rich Tumor. Cancer Res. 2016;76:6266-6277 pubmed
    ..Cancer Res; 76(21); 6266-77. ©2016 AACR. ..
  2. Teng M, Ngiow S, Ribas A, Smyth M. Classifying Cancers Based on T-cell Infiltration and PD-L1. Cancer Res. 2015;75:2139-45 pubmed publisher
    ..We review this stratification and the latest in a series of results that shed light on new approaches for rationally designing ideal combination cancer therapies based on tumor immunology. ..
  3. Mittal D, Vijayan D, Putz E, Aguilera A, Markey K, Straube J, et al. Interleukin-12 from CD103+ Batf3-Dependent Dendritic Cells Required for NK-Cell Suppression of Metastasis. Cancer Immunol Res. 2017;5:1098-1108 pubmed publisher
    ..i>Cancer Immunol Res; 5(12); 1098-108. ©2017 AACR. ..
  4. Viel S, Marçais A, Guimaraes F, Loftus R, Rabilloud J, Grau M, et al. TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway. Sci Signal. 2016;9:ra19 pubmed publisher
    ..Moreover, we propose that boosting the metabolic activity of antitumor lymphocytes could be an effective strategy to promote immune-mediated tumor suppression. ..
  5. O Donnell J, Teng M, Smyth M. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2018;: pubmed publisher
  6. Mittal D, Vijayan D, Smyth M. Overcoming Acquired PD-1/PD-L1 Resistance with CD38 Blockade. Cancer Discov. 2018;8:1066-1068 pubmed publisher
    ..i>Cancer Discov; 8(9); 1066-8. ©2018 AACRSee related article by Chen et al., p. 1156. ..
  7. Ferrari de Andrade L, Ngiow S, Stannard K, Rusakiewicz S, Kalimutho M, Khanna K, et al. Natural killer cells are essential for the ability of BRAF inhibitors to control BRAFV600E-mutant metastatic melanoma. Cancer Res. 2014;74:7298-308 pubmed publisher
    ..Overall, this study supports the idea that additional NK cell-based immunotherapy (by checkpoint blockade or agonists or cytokines) may combine well with BRAF(V600E) inhibitor therapy to promote more durable responses in melanoma. ..
  8. Bald T, Smyth M. TGF? shuts the door on T cells. Br J Cancer. 2018;119:1-3 pubmed publisher
    ..These studies indicate that TGF? enables T cell exclusion in a proportion of colorectal and urothelial cancers, and in the latter disease may reduce their response to anti-PD-L1 immunotherapy. ..
  9. Ngiow S, McArthur G, Smyth M. Radiotherapy complements immune checkpoint blockade. Cancer Cell. 2015;27:437-8 pubmed publisher
    ..The superior activity of radiation and dual immune checkpoint blockade is mediated by non-redundant immune mechanisms in cancer. ..

More Information


  1. Guillerey C, Smyth M. NK Cells and Cancer Immunoediting. Curr Top Microbiol Immunol. 2016;395:115-45 pubmed publisher
    ..Herein, we review the current knowledge of NK cell functions in anti-tumor immunity . We discuss NK cell activity in the cancer immunoediting process with particular emphasis on the elimination and escape phases. ..
  2. Guillerey C, Harjunpää H, Carrié N, Kassem S, Teo T, Miles K, et al. TIGIT immune checkpoint blockade restores CD8+ T cell immunity against multiple myeloma. Blood. 2018;: pubmed publisher
    ..Altogether our data provide evidence for an immune-inhibitory role of TIGIT in MM and support the development of TIGIT-blocking strategies for the treatment of MM patients. ..
  3. Mittal D, Young A, Stannard K, Yong M, Teng M, Allard B, et al. Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor. Cancer Res. 2014;74:3652-8 pubmed publisher
    ..Overall, these results provide a strong rationale to use A2ARi with anti-PD-1 mAb for the treatment of minimal residual and metastatic disease. ..
  4. Mittal D, Sinha D, Barkauskas D, Young A, Kalimutho M, Stannard K, et al. Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis. Cancer Res. 2016;76:4372-82 pubmed publisher
    ..Collectively, high A2BR on mouse and human tumors promotes cancer metastasis and is an ideal candidate for therapeutic intervention. Cancer Res; 76(15); 4372-82. ©2016 AACR. ..
  5. Nakamura K, Kassem S, Cleynen A, Chrétien M, Guillerey C, Putz E, et al. Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment. Cancer Cell. 2018;33:634-648.e5 pubmed publisher
    ..Strikingly, high levels of bone marrow plasma IL-18 were associated with poor overall survival in MM patients. Furthermore, our preclinical studies suggested that IL-18 could be a potential therapeutic target in MM. ..
  6. Blake S, Stannard K, Liu J, Allen S, Yong M, Mittal D, et al. Suppression of Metastases Using a New Lymphocyte Checkpoint Target for Cancer Immunotherapy. Cancer Discov. 2016;6:446-59 pubmed publisher
    ..Targeting host CD96 is shown to complement surgery and conventional immune checkpoint blockade. ..
  7. Ngiow S, Loi S, Thomas D, Smyth M. Mouse Models of Tumor Immunotherapy. Adv Immunol. 2016;130:1-24 pubmed publisher
    ..We will also highlight some recent advances in experimental modeling of human malignancies in mice that are leading towards personalized therapy in patients. ..
  8. Austin R, Smyth M, Lane S. Harnessing the immune system in acute myeloid leukaemia. Crit Rev Oncol Hematol. 2016;103:62-77 pubmed publisher
    ..Understanding immune responses to AML has implications for the development and use of immunotherapies to treat AML patients with distinct genetic abnormalities. ..
  9. Guillerey C, Nakamura K, Vuckovic S, Hill G, Smyth M. Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies. Cell Mol Life Sci. 2016;73:1569-89 pubmed publisher
    ..Finally, we detail the numerous promising immune-targeting strategies approved or in clinical trials for the treatment of MM. ..
  10. request reprint
    Blake S, Dougall W, Miles J, Teng M, Smyth M. Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy. Clin Cancer Res. 2016;22:5183-5188 pubmed
    ..This review will examine the rationale behind targeting CD96 and TIGIT, and discuss the potential approaches in translating these preclinical findings into novel clinical agents. Clin Cancer Res; 22(21); 5183-8. ©2016 AACR. ..
  11. Mittal D, Gubin M, Schreiber R, Smyth M. New insights into cancer immunoediting and its three component phases--elimination, equilibrium and escape. Curr Opin Immunol. 2014;27:16-25 pubmed publisher
  12. Young A, Mittal D, Stagg J, Smyth M. Targeting cancer-derived adenosine: new therapeutic approaches. Cancer Discov. 2014;4:879-88 pubmed publisher
    ..This brief review delineates the current treatment strategies and tumor subtypes that will benefit from targeting adenosinergic pathways, alone or in combination with contemporary approaches to cancer treatment. ..
  13. Martinet L, Ferrari de Andrade L, Guillerey C, Lee J, Liu J, Souza Fonseca Guimaraes F, et al. DNAM-1 expression marks an alternative program of NK cell maturation. Cell Rep. 2015;11:85-97 pubmed publisher
    ..Collectively, our data reveal the existence of a functional program of NK cell maturation marked by DNAM-1 expression. ..
  14. Souza Fonseca Guimaraes F, Young A, Mittal D, Martinet L, Bruedigam C, Takeda K, et al. NK cells require IL-28R for optimal in vivo activity. Proc Natl Acad Sci U S A. 2015;112:E2376-84 pubmed publisher
  15. Young A, Ngiow S, Gao Y, Patch A, Barkauskas D, Messaoudene M, et al. A2AR Adenosine Signaling Suppresses Natural Killer Cell Maturation in the Tumor Microenvironment. Cancer Res. 2018;78:1003-1016 pubmed publisher
    ..b>Significance: Ablating adenosine signaling is found to promote natural killer cell maturation and antitumor immunity and reduce tumor growth. Cancer Res; 78(4); 1003-16. ©2017 AACR. ..
  16. Ngiow S, Young A, Jacquelot N, Yamazaki T, Enot D, Zitvogel L, et al. A Threshold Level of Intratumor CD8+ T-cell PD1 Expression Dictates Therapeutic Response to Anti-PD1. Cancer Res. 2015;75:3800-11 pubmed publisher
    ..Our analyses provide a framework to interrogate intratumor CD8(+) T-cell PD1 and immune PDL1 levels and response in human cancer. ..
  17. Young A, Ngiow S, Madore J, Reinhardt J, Landsberg J, Chitsazan A, et al. Targeting Adenosine in BRAF-Mutant Melanoma Reduces Tumor Growth and Metastasis. Cancer Res. 2017;77:4684-4696 pubmed publisher
    ..Our results suggest that targeting adenosine may enhance therapeutic responses for melanoma patients receiving targeted or immune-based therapies. Cancer Res; 77(17); 4684-96. ©2017 AACR. ..
  18. Ahern E, Harjunpää H, Barkauskas D, Allen S, Takeda K, Yagita H, et al. Co-administration of RANKL and CTLA4 Antibodies Enhances Lymphocyte-Mediated Antitumor Immunity in Mice. Clin Cancer Res. 2017;23:5789-5801 pubmed publisher
    ..i>Clin Cancer Res; 23(19); 5789-801. ©2017 AACR. ..
  19. O Donnell J, Long G, Scolyer R, Teng M, Smyth M. Resistance to PD1/PDL1 checkpoint inhibition. Cancer Treat Rev. 2017;52:71-81 pubmed publisher
  20. Mittal D, Caramia F, Michiels S, Joensuu H, Kellokumpu Lehtinen P, Sotiriou C, et al. Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells. Cancer Res. 2016;76:264-74 pubmed publisher
    ..Collectively, our findings suggest that elevating IL21 signaling may enhance trastuzumab efficacy, thus constituting a novel candidate strategy to overcome trastuzumab resistance and improve patient survival. Cancer ..
  21. Young A, Ngiow S, Barkauskas D, Sult E, Hay C, Blake S, et al. Co-inhibition of CD73 and A2AR Adenosine Signaling Improves Anti-tumor Immune Responses. Cancer Cell. 2016;30:391-403 pubmed publisher
    ..In a two-way mixed leukocyte reaction using a fully human anti-CD73, we demonstrated that Fc receptor binding augmented the production of proinflammatory cytokines. ..
  22. Teng M, Khanna R, Smyth M. Checkpoint Immunotherapy: Picking a Winner. Cancer Discov. 2016;6:818-20 pubmed publisher
    ..Cancer Discov; 6(8); 818-20. ©2016 AACR.See related article by Chen et al., p. 827. ..