Evgeniy B. Eruslanov, PhD - Thoracic Surgery

Ongoing Research Support

Dr. Eruslanov’s group focuses on understanding how tumor-associated neutrophils (TAN) and macrophages (TAM) are integrated in the regulation of effector mechanisms of the innate and adaptive immune systems in lung cancer patients. In close collaboration with Dr. Sunil Singhal and Dr. Steven M. Albelda, our team is currently investigating the:

  • Regulation of the tumor-specific T cell response by TAN and TAM subpopulations in human lung tumor
  • Differentiation and polarization of immature neutrophils in the tumor microenvironment using the novel in vitro model of long-lived human bone marrow neutrophils
  • Role of tumor-infiltrating FcR-bearing cells in mediating an antibody-dependent tumor cell cytotoxicity in human lung tumors

The impact of our work lies in developing a fundamental understanding of how intratumoral neutrophils and macrophages are linked to the biology of human lung cancers. Understanding how to steer the phenotype of TANs and TAMs towards anti-tumor effector cells will open new therapeutic options in the future design of active immunotherapy to enhance current cancer treatments.

Publications

Research Publications, Peer Reviewed

  1. Maisel K, Merrilees MJ, Atochina-Vasserman EN, Lian L, Obraztsova K, Rue R, Vasserman AN, Zuo N, Angel LF, Gow AJ, Kang I, Wight TN, Eruslanov E, Swartz MA, Krymskaya VP. Immune checkpoint ligand PD-L1 is upregulated in pulmonary lymphangioleiomyomatosis (LAM). Am J Respir Cell Mol Biol. 2018 Aug 10
  2. Negorev D, Beier UH, Zhang T, Quatromoni JG, Bhojnagarwala P, Albelda SM, Singhal S, Eruslanov E, Lohoff FW, Levine MH, Diamond JM, Christie JD, Hancock WW, Akimova T. Human neutrophils can mimic myeloid-derived suppressor cells (PMN-MDSC) and suppress microbead or lectin-induced T cell proliferation through artefactual mechanisms. Science Reports, 2018, Feb 16;8(1):3135.
  3. Bruno T, Ebner P, Moore B, Squalls O, Waugh K, Eruslanov E, Singhal S, Mitchell J, Franklin W, Merrick D, McCarter M, Palmer B, Kern J, and Jill Slansky. Antigen-presenting tumor B cells affect CD4+TIL phenotype in non-small cell lung cancer patients. Cancer Immunology Research, 2017, Oct5;(10): 898-907.
  4. Akimova T, Zhang T, Negorev D, Singhal S, Stadanlick J, Rao A, Annunziata M, Levine M, Beier U, Diamond J, Christie J, Albelda S, Eruslanov E, and Hancock W. Tumor Treg upregulate a quartet of “Treg-locking” transcription factors. JCI Insight, 2017; 2(16): e94075.
  5. Eruslanov E. Phenotype and function of tumor-associated neutrophils and their subsets in early-stage human lung cancer. Cancer Immunology, Immunotherapy. 2017, Aug; 66(8): p997-1006
  6. Eruslanov E, Singhal S, and Albelda S. Mouse versus Human Neutrophils in Cancer: A Major Knowledge Gap. Trends in Cancer. 2017, Vol. 3, No. 2, p149-160
  7. Stephen TL, Payne KK,Chaurio RA, Allegrezza MJ, Zhu H, Perez-Sanz J, Perales-Puchalt A, Nguyen JM, Vara-Ailor AE, Eruslanov E, Borowsky ME, Zhang R, Laufer TM, Conejo-Garcia JR. SATB1 Expression Governs Epigenetic Repression of PD-1 in Tumor-Reactive T Cells. Immunity. 2017, Volume 46, Issue 1, 17, p51–64
  8. Allegrezza MJ, Rutkowski MR, Stephen TL, Svoronos N, Perales-Puchalt A, Nguyen JM, Payne KK, Singhal S, Eruslanov E, Tchou J, Conejo-Garcia JR. Trametinib Drives T-cell-Dependent Control of KRAS-Mutated Tumors by Inhibiting Pathological Myelopoiesis. Cancer Research. 2016 Nov 1; 76(21): p6253-6265.
  9. Svoronos N, Perales-Puchalt A, Allegrezza MJ, Rutkowski MR, Payne KK, Tesone AJ, Nguyen JM, Curiel TJ, Cadungog MG, Singhal S, Eruslanov E, Zhang P, Tchou J, Zhang R, Conejo-Garcia JR. Tumor Cell-Independent Estrogen Signaling Drives Disease Progression through Mobilization of Myeloid-Derived Supressor Cells. Cancer Discovery. 2017 Jan;7(1):p72-85.
  10. T Condamine, G. Dominguez, Je-In Youn, A. Kossenkov, S Mony, KAlicea-Torres, E Tcyganov, A Hashimoto, Y Nefedova, C Lin, S Partlova, A Garfall, D. Vogl, X Xu, S Knight, G Malietzis, G Han Lee, E Eruslanov, S Albelda, X Wang, J Mehta, M Bewtra, A Rustgi, N Hockstein, R Witt, G Masters, B Nam, D Smirnov, M Sepulveda and D Gabrilovich.
 Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Science Immunology. 2016, Aug; 1(2), DOI: 10.1126/sciimmunol.aaf8943
  11. Singhal S, Bhojnagarwala P, O’Brien S, Moon E, Garfall A, Rao A,. Quatromoni J, Stephen T, Litzky L, Deshpande D, Feldman M, Hancock W, Conejo-Garcia J, Albelda S, and Eruslanov E. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen Presenting Cell Features in Early-Stage Human Lung Cancer. Cancer Cell, 2016, Jun 30. doi: 10.1016/j.ccell.2016.06.001
  12. Moon E, Ranganathan R, Eruslanov E, Kim S, Newick K, O'Brien S, Lo A, Liu X, Zhao Y, and Albelda S. Blockade of Programmed Death 1 Augments the Ability of Human T cells Engineered to Target NY-ESO-1 to Control Tumor Growth after Adoptive Transfer. Clinical Cancer Research; 2016 Jan 15;22(2):436-47. doi: 10.1158/1078-0432.CCR-15-1070.
  13. Karakasheva TA, Waldron TJ, Eruslanov E, Lee JS, O'Brien S, Hicks PD, Basu D, Singhal S, Malavasi F, Rustgi AK. CD38-Expressing Myeloid-Derived Suppressor Cells Promote Tumor Growth in a Murine Model of Esophageal Cancer. Cancer Research, 2015 Oct 1;75(19):4074-85. doi: 10.1158/0008-5472.
  14. Eruslanov E (corresponding author), Bhojnagarwala P, Quatromoni J, Stephen T, Ranganathan A, Deshpande C, Akimova T, Vachani A, Litzky L, Hancock W, Conejo-Garcia J, Feldman M, Albelda S, and Singhal S. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. The Journal of Clinical Investigation, 2014, Dec 1; 124(12): 5466-80, highlighted as a featured paper
  15. Quatromoni JG, Singhal S, Bhojnagarwala P, Hancock WW, Albelda SM, Eruslanov E. An optimized disaggregation method for human lung tumors that preserves the phenotype and function of the immune cells. J Leukoc Biol. 2015 Jan; 97(1):201-9.
  16. Holt D, Okusanya O, Judy R, Venegas O, Jiang J, DeJesus E, Eruslanov E, Quatromoni J, Bhojnagarwala P, Deshpande C, Albelda S, Nie S, Singhal S. Intraoperative near-infrared imaging can distinguish cancer from normal tissue but not inflammation. PLoS One. 2014 Jul 29; 9(7):e103342.
  17. Quatromoni JG, Predina JD, Bhojnagarwala P, Judy RP, Jiang J, De Jesus EM, Kapoor V, Cheng G, Okusanya OT, Eruslanov E, Singhal S. Adenoviral-based immunotherapy provides local disease control in an orthotopic murine model of esophageal cancer. J Immunother. 2014 Jun; 37(5):283-92.
  18. Akimova T, Xiao H, Liu Y, Bhatti TR, Jiao J, Eruslanov E, Singhal S, Wang L, Han R, Zacharia K, Hancock WW, Beier UH. Targeting sirtuin-1 alleviates experimental autoimmune colitis by induction of Foxp3+ T-regulatory cells. Mucosal Immunology. 2014 Feb 19.
  19. Mishalian I, Bayuh R, Eruslanov E, Michaeli J, Levy L, Zolotarov L, Singhal S, Albelda SM, Granot Z, Fridlender ZG. Neutrophils recruit regulatory T-cells into tumors via secretion of CCL17-A new mechanism of impaired antitumor immunity. International Journal of Cancer. 2014 Feb 6. doi: 10.1002/ijc.28770. [Epub ahead of print]
  20. Quatromoni JG, Suzuki E, Okusanya O, Judy BF, Bhojnagarwala P, Venegas O, Eruslanov E, Predina JD, Albelda SM, Singhal S. The timing of TGF-β inhibition affects the generation of antigen-specific CD8+ T cells. BMC Immunol. 2013 Jul 17; 14:30
  21. Eruslanov E, Stoffs T, Kim W, Daurkin I, Gilbert S, Su LM, Vieweg J, Daaka Y, and Kusmartsev S. Expansion of CCR8+ inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas. Clinical Cancer Research 2013, Apr 1; 19(7):1670-80.
  22. Predina J, Eruslanov E, Judy B, Kapoor V, Cheng G, Wang LC, Sun J, Moon EK, Fridlender ZG, Albelda S, Singhal S. Changes in the local tumor microenvironment in recurrent cancers may explain the failure of vaccines after surgery. Proceedings of the National Academy of Sciences USA Dec. 27, 2012 Jan 29; 110 (5): E415-24
  23. Quatromoni JG, Eruslanov E. Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer. Am. J. Transl. Res. 2012; 4(4): 376-89.
  24. Daurkin I*, Eruslanov E* (*equally contributed), Stoffs T, Perrin GQ, Algood C, Gilbert SM, Rosser CJ, Su LM, Vieweg J, and Kusmartsev S. Tumor-associated macrophages mediate immune suppression in the renal cancer microenvironment by activating the 15-lipoxygenase-2 pathway. Cancer Research, 2011 Oct 15; 71(20): 6400-9
  25. Eruslanov E, Neuberger M, Daurkin I, Rosser C, Perrin G, Algood C, Dahm P, Vieweg J, Gilbert S and Kusmartsev S. Circulating and tumor-infiltrating myeloid cell subsets in patients with bladder cancer, International Journal of Cancer, 2012 Mar 1; 130 (5): 1109-19
  26. Eruslanov E, Daurkin I, Vieweg J, Daaka Y, and Kusmartsev S. Aberrant PGE2 metabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells. International Immunopharmacology, 2011, 11(7): 845-52.
  27. Eruslanov E, Daurkin I, Ortiz J, Vieweg J, and Kusmartsev S. Pivotal Advance: Tumor-mediated induction myeloid-derived suppressor cells and M2-polarized macrophage by altering intracellular PGE2 metabolism in myeloid cells. Journal of Leukocyte Biology, 2010, 88(5): 839-48
  28. Eruslanov E, Kusmartsev S. Identification of ROS using oxidized DCFDA and flow-cytometry. Methods Mol Biol. 2010; 594: 57-72.
  29. Daurkin I, Eruslanov E, Vieweg J, Kusmartsev S. Generation of antigen presenting cells from tumor-infiltrated CD11b myeloid cells with DNA demethylating agent 5-aza-2'-deoxycytidine. Cancer Immunol. Immunother. 2010, 59(5): 697-706
  30. Porvasnik S, Sakamoto N, Kusmartsev S, Eruslanov E, Kim WJ, Cao W, Urbanek C, Wong D, Goodison S, Rosser CJ. Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth. Prostate. 2009. Sep 15;69(13):1460-9.
  31. Glushakova LG, Lisankie MJ, Eruslanov EB, Ojano-Dirain C, Zolotukhin I, Liu C, Srivastava A, Stacpoole PW. AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene causes metabolic remodeling and apoptosis of human liver cancer cells. Mol. Genet. Metab. 2009, Nov, 98(3): 289-99
  32. Eruslanov E, Kaliberov S, Daurkina I, Kaliberova L, Buchsbaum D, Vieweg J, Kusmartsev S. Altered expression of 15-prostaglandin dehydrogenase in intra-tumoral CD11b myeloid cells: a new mechanism of immune evasion in cancer. J. Immunology. 2009. Jun15; 182(12): 7548-57
  33. Kusmartsev S, Su Z, Heiser A, Dannull J, Eruslanov E, Kübler H, Yancey D, Dahm P. and Vieweg J. Reversal of myeloid cell-mediated immunosuppression in patients with metastatic renal cell carcinoma. Clinical Cancer Research. 2008. Dec 15:14(24): 8270-8278
  34. Sakai Y., Goodison S., Kusmartsev S., Fletcher B., Eruslanov E., Cao W., Porvasnik S., Namiki K, Anai S., Rosser CJ. Bcl-2 mediated modulation of vascularization in prostate cancer xenografts. Prostate. 2009, Apr 1: 69(5): 459-70.
  35. S. Kusmartsev, E. Eruslanov, H. Kübler, T. Tseng, Y. Sakai, Z. Su, S. Kaliberov, C. Rosser, P. Dahm, D. Siemann and Johannes Vieweg. Oxidative Stress Regulates Expression of VEGFR1 in Myeloid Cells: Link to Tumor-Induced Immune Suppression in Renal Cell Carcinoma. J. Immunology. 2008. Jul 1; 181(1): 346-53
  36. Yan BS, Pichugin AV, Jobe O, Helming L, Eruslanov EB, Gutierrez-Pabello JA, Rojas M, Shebzukhov YV, Kobzik L, and Kramnik I. Progression of Pulmonary Tuberculosis and Efficiency of Bacillus Calmette-Guerin Vaccination are Genetically Controlled via a Common sst1-Mediated Mechanism of Innate Immunity. J. Immunology. 2007, Nov 15; 179(10): 6919-32
  37. Pan H, Mostoslavky G, Eruslanov E, Kotton DN, Kramnik I. Dual-promoter lentiviral system allows inducible expression of noxious proteins in macrophages. J Immunological Methods. 2008, Jan 1; 329 (1-2): 31-34
  38. Orlova MO, Majorov KB, Laydova IV, Eruslanov EB, M’lan CE, Greenwood CM, Shurr E and Apt AS. Constitutive differences in gene expression profiles parallel genetic patterns of susceptibility to tuberculosis in mice. Infection and Immunity. 2006 Jun; 74(6): 3668-72.
  39. K. B Majorov, E. B. Eruslanov, E.I. Rubakova, T. K. Kondratieva, and A. S. Apt. Analysis of cellular phenotypes that mediate genetic resistance to tuberculosis using a radiation bone marrow chimera approach. Infection and Immunity. 2005, Sep, 73(9): 6174-8.
  40. E. B. Eruslanov, I. V. Lyadova, T. K. Kondratieva, K. B Majorov, I.V Scheglov, M. O. Orlova, and A. S. Apt. Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice. Infection and Immunity. 2005, Mar; 73(3): 1744-53
  41. Mischenko VV, Kapina MA, Eruslanov EB, Kondratieva EV, Lyadova IV, Young DB, Apt AS. Mycobacterial dissemination and cellular responses after 1-lobe restricted tuberculosis infection of genetically susceptible and resistant mice. J. Infect. Dis. 2004 Dec 15; 190 (12): 2137-45.
  42. E. B. Eruslanov, K. B Majorov, M. O. Orlova, V. V. Mischenko, T. K. Kondratieva, A. S. Apt and I. V. Lyadova. Lung cell responses to M. tuberculosis in genetically susceptible and resistant mice following intratracheal challenge. Clin. Exp. Immunol., 2004, 135:19-28.
  43. K. B. Majorov, I. V. Lyadova, T. K. Kondratieva, E. B. Eruslanov, E. I. Rubakova, M. O. Orlova, V. V. Mischenko, and A. S. Apt. Different innate ability of I/St and A/Sn mice to combat virulent M. tuberculosis: phenotypes expressed in lung and extra-pulmonary macrophages. Infect. Immunity 2003, 71: 697-707.
  44. V. Lyadova, H. M. Vordermeier, E. B. Eruslanov, S. V. Khaidukov, A. S. Apt, R. G. Hewinson. Intranasal BCG vaccination protects BALB/c mice against virulent Mycobacterium bovis and accelerates production of IFN-γ in their lungs. Clin. Exp. Immunol., 2001, 126:274-279.
  45. Lyadova I. V., E. B. Eruslanov, V. V. Yeremeev, K. B. Majorov, B. V. Nikonenko, A. V. Pichugin, S. V. Khaidukov, T. K. Kondratieva, A. S. Apt. Comparative analysis of T lymphocytes recovered from the lungs of mice genetically susceptible, resistant and hyperresistant to Mycobacterium tuberculosis-triggered disease. J. Immunology. 2000, 165:5921-5931.

Editorials, Chapters, Case Reports & Books

  1. Eruslanov E. Kusmartsev S.  Identification of ROS using oxidized DCFDA and flow cytometry.”  Part I, Chap. 4 in Walker JM (ed.) and Armstrong DD (vol. ed.): Methods in Molecular Biology, Volume “Advanced Protocol in Oxidative Stress II.”  New York: Humana Press/ Springer, Vol. 594, 2010, 57-72.

Invited talks

  1. National Allergy and Infectious Diseases (NIAID), “Suppressor cell and TB”, Rockville, Maryland, January 16, 2019
  2. Cold Spring Harbor Laboratory, Banbury meeting, “Diverse Functions of Neutrophils in Cancer”, LIoyd Harbor, New York, November 27-30, 2018
  3. Pulmonary-A&I Research Conference, University of Pennsylvania, October 31, 2018
  4. Janssen Inc. Inflammasome symposium, Antwerp, Belgium, October 17-18, 2018
  5. University of Burgundy, Lipids, Nutrition, Cancer annual seminar, Dijon, France, May 24th, 2018
  6. Fox Chase Cancer Center, Inflammation Working Group. Philadelphia, January 31st , 2018.
  7. Fall seminars of The Division of Transplant Immunobiology and the Department of Pathology and Laboratory Medicine at the Children’s Hospital of Philadelphia. Philadelphia, September 20th, 2017.
  8. American Association of Immunologists (AAI) annual meeting Immunology 2017, Major Symposium F: Neutrophils Function in Autoimmunity, Infection, and Cancer. May 12-16, Washington, D.C. E. Eruslanov. Tumor-associated neutrophils with antigen-presenting cell features in human lung cancer
  9. Immuno-oncology seminar, Translational Genomics Research Institute, Phoenix, April 25-26.
  10. Immuno-oncology seminar, AstraZeneca, Waltham, MA, 2017, March 16.
  11. Inflammation, Immunity and Cancer: The Society For Leukocyte Biology’s 49th Annual Meeting and “Neutrophil 2016”: Neutrophils and Other Leukocytes, Major Symposium. University of Verona, Verona, Italy, September 15-17, 2016,
  12. Regulatory Myeloid Suppressor Cells Conference, Philadelphia, The Wistar Institute, June 16-19, 2016
  13. Immunology School “Regulation of Lung Inflammation”, Moscow, Russia, May11-13, 2016.
  14. Immuno-oncology seminar, Janssen Inc, Spring House, March 12, 2016.
  15. University of Pennsylvania LAM Symposium “ Lymphatics Lymphangiogenesis, and VEGF-D: Targets for LAM”, Philadelphia, PA, Feb 17, 2015.
  16. University of Pennsylvania Respiration Research Retreat, June 13, 2014

Grant Review Activities

  1. Israel Science Foundation (ISF), Ad Hoc Reviewer, 2015-present
  2. Cancer Research UK, Ad Hoc Reviewer, 2015-present
  3. French National Cancer Institute, Ad Hoc Reviewer, 2016-present
  4. Belgium Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek - Vlaanderen, FWO), Ad Hoc Reviewer 2016-present
  5. Medical Research Councils UK (RCUK), UK, Ad Hoc Reviewer 2016-present

Manuscript reviewer for

  1. Cancer Cell, Journal of Clinical Investigation, Nature Communications, Cancer Discovery, Cancer Research, Clinical Cancer Research, Cancer Immunology Research, European Journal of Immunology, Cancer Immunology and Immunotherapy, Journal of Leukocyte Biology.

Grant Support

Current:
1. Department of Defense-LC140199, Career Development Award, W81XWH-15-1-0717
2015 -2018
Role: PI

2. NIH/NCI R01 CA187392-01A1,
2015-2020
Title: Tumor-associated neutrophils in human lung cancer.
Role: PI

3. NIH/NCI, R01 CA187392-01A11-R01-HL-131626-01
2016-2020
Title: Lymphangiogenesis in Pulmonary Lymphangioleiomyomatosis (LAM)
Role: Co-I (Dr. Krymskaya-PI)

4. Department of Defense -LC140042
2015 -2017
Title: Targeted Repolarization of Tumor-Associated Macrophages in Lung Cancer
Role: Co-I (Dr. Singhal-PI)

5. Janssen Pharmaceuticals, Inc./ Johnson & Johnson
2016-2017
Title: Evaulation of the Human Lung Cancer Immune Microenvironment
Role: Co-PI (Dr. Albelda-PI)

6. Incyte Inc.
2017-2019
Eruslanov’s aim: The role of PI3K and JAK pathways on the capacity of lung tumor-derived factors to alter macrophage differentiation, effector functions (including ADP and ADCC) and T cell suppressive activity
Role: Co-PI (Dr. Albelda-PI)