Inflammation related complications in non-cancerous and cancerous diseases

Chronic inflammation arising in various non-cancerous and cancerous diseases leads to an abnormal immunity and exposes patients to a variety of complications. These include suppression of the immune system, tissue damage, cardiovascular diseases and initiation of malignancies. It is important to note that chronic inflammation is considered as the “secret killer” as it operates within our body with no signs until complications appear. It is similar to a volcano. In cases of volcano related concerns, seismographs are needed to sense the worsening of the situation before the volcano bursts! Similarly, immune biomarkers, which are the seismographs of the immune system functionality, are needed to sense the immune status of patients and accordingly, direct the physician to apply the suitable type of treatment to avoid complications and health deterioration. During the years we discovered a set of immune biomarkers that could sense the individual’s immune system functionality and developed the detection technology. With these tools in hand, we could fulfill the clinical needs for monitoring the immune status of patients suffering from noncancerous and cancerous chronic diseases. We clinically applied our new technology and proof the concept in clinical studies that with the technology we developed we could achieve the following: 1) evaluate of the host’s immune system function and distinguish between acute (beneficial response) and chronic (harmful response) inflammation, 2) predict responses to immune-based therapies applied today in cancer patients (as shown for melanoma patients treated with ipilimumab) and direct the type of treatment – published in Clinical Cancer research, 3) detect disease regression or progression and directing the physician of which type of chemotherapy to give to CRC patients and follow responses – published in Cancer Research, and 4) predict the appearance of complications before they are evident as shown in diabetic patients. Monitoring such immune system biomarkers is expected to have a major clinical impact in addition to unraveling the entangled complexity underlying abnormal immunity that is evident during chronic inflammation. Thus, newly discovered biomarkers and those that are currently under investigation are projected to open a new era towards combating the silent damage induced by chronic inflammation.

• Chronic inflammation-induced immunosuppressive cells and the gut microbiota as intruders supporting colorectal cancer
• polarized myeloid derived suppressor cells during chronic inflammation are skewed towards osteoclast differentiation and cause bone loss
• The molecular network governing myeloid polarization towards highly suppressive cell.
• Harmful MDSCs and B cell interaction in the heart of chronic inflammation induced immunosuppression.
• Protection of T and NK cells from myeloid cells-induced immunosuppression.

1. Baniyash, M., Sade-Feldman, M., and Kanterman J. (2014) Chronic inflammation and cancer: Suppressing the suppressors. Cancer Immunol Immunother. 63:11-20.
2. Klieger, Y., Almogi-Hazan, O., Ish-Shalom, E., Pato, A., Pauker, MH., Barda-Saad, M., Wang L., and Baniyash M. (2014) Unique z-chain motifs mediate a direct TCR-actin linkage critical for immunological synapse formation and T-cell activation. EJI. 44:58-68.
3. Kanterman, J., Sade-Feldman, M, Biton, M, Lasry, A., Ish-Shalom, E., Hubert, A., and Baniyash M. (2014) Adverse Immunoregulatory Effects of 5FU and CPT11 Chemotherapy on Myeloid-Derived Suppressor Cells and Colorectal Cancer Outcomes. Cancer Res. 74:6022-6035.
4. Hefetz-Sela S, Stein I, Klieger Y, Porat R, Sade-Feldman M, Zreik F, Nagler A, Pappo O, Quagliata L, Dazert E, Eferl R, Terracciano L, Wagner EF, Ben-Neriah Y, Baniyash M, Pikarsky E. (2014) Acquisition of an immunosuppressive pro-tumorigenic macrophage phenotype depending on c-Jun phosphorylation. Proc Natl Acad Sci U S A. 111:17582-17587.
5. Eldor R, Klieger Y, Sade-Feldman M, Vaknin I, Varfolomeev I, Fuchs C and Baniyash M. (2015) CD247, a Novel T-Cell Derived Diagnostic and Prognostic Biomarker for Detecting Disease Progression and Severity in Patients With Type 2 Diabetes Mellitus. Diabetes Care. 38:113-8.
6. Meirow Y, Kanterman J, Baniyash M. (2015) Paving the Road to Tumor Development and Spreading: Myeloid-Derived Suppressor Cells are Ruling the Fate. Invited review. Front Immunol. 6:523-535.
7. Ish-Shalom E, Meirow Y, Sade-Feldman M, Kanterman J, Wang L, Olga Mizrahi O, Yair Klieger Y and Baniyash M. (2016) Impaired SNX9 expression in immune cells during chronic inflammation: prognostic and diagnostic implications. Under revision in J. Immunol. 196:156-67.
8. Tarcic O, Pateras IS, Cooks T, Shema E, Kanterman J, Ashkenazi H, Boocholez H, Hubert A, Rotkopf R, Baniyash M, Pikarsky, Gorgoulis VG, Oren M. (2016) RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer. Cell Rep. 14:1462-76.
9. Sade-Feldman M, Kanterman J, Keliger Y, Ish-Shalom E, Mizrahi O, Saragovi A, Shtainberg H, Lotem M, and Baniyash M. (2016) Clinical significance of circulating CD33+CD11b+HLA-DR- myeloid cells in Stage-IV melanoma patients treated with ipilimumab. Clin Cancer Res, 65:857-67.
10. Baniyash M. (2016) Myeloid derived suppressor cells as intruders and targets: Clinicalimplications in cancer therapy. Invited review. Cancer Immunol Immunother, 65:857-67.
11. Meirow, Y., Vaknin, I. and Baniyash M (2011-2016) Inflammatory response and immunity. Encyclopedia of Cancer. Editors: Manfred Schwab, Springer publication
12. Mizrahi O, Ish Shalom E, Baniyash M, Klieger Y. (2017) Quantitative flow cytometry: Concerns and recommendations in clinic and research. Cytometry B Clin Cytom. Feb 11.
13. Meirow Y, Baniyash M (2017). Immune biomarkers for chronic inflammation related complications in noncancerous and cancerous diseases. Cancer Immunol Immunother. 2017 Jul 3. doi: 10.1007/s00262-017-2035-6.
14. Ben-Meir K, Twaik N Baniyash M (2018). Plasticity and biological diversity of myeloid derived
    suppressor cells. Current Opinion in Immunology 2018, 51:154–161
15. Ashkenazi-Preiser, Hadas, Ivan Mikula Jr, and Michal Baniyash. “The diverse roles of myeloid derived suppressor cells in mucosal immunity.” Cellular Immunology (2021): 104361.
16. Maimon, A., Levi-Yahid, V., Ben-Meir, K., Halpern, A., Talmi, Z., Priya, S., Mizraji, G., Mistriel-Zerbib, S., Berger, M., Baniyash, M. and Loges, S., 2021. Myeloid cell–derived PROS1 inhibits tumor metastasis by regulating inflammatory and immune responses via IL-10. The Journal of Clinical Investigation, 131(10).
17. Meirow, Y., Jovanovic, M ,K. J. Krijgsveld, N. Levaot & M. Baniyash, Bone Research volume 10, Article number: 36 (2022) Cite this article Y. et al. Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss. Bone Res 10, 36 (2022). https://doi.org/10.1038/s41413-022-00206-z
18. Kerem Ben‐Meir, Nira Twaik, Yaron Meirow, Michal Baniyash, An In Vivo Mouse Model for Chronic Inflammation–Induced Immune Suppression: A “Factory” for Myeloid‐Derived Suppressor Cells (MDSCs), Current Protocols, 10.1002/cpz1.558, 2, 10, (2022).Wiley Online Library
19. Or Reuven, Ivan Mikula, Hadas Ashkenazi‐Preiser, Nira Twaik, Kerem Ben‐Meir, Yaron Meirow, Leonor Daniel, Guy Kariv, Mahdi Kurd, Michal Baniyash, Functional Assays Evaluating Immunosuppression Mediated by Myeloid‐Derived Suppressor Cells, Current Protocols, 10.1002/cpz1.557, 2, 10, (2022).Wiley Online Library
20. Or Reuven, Ivan Mikula, Hadas Ashkenazi‐Preiser, Nira Twaik, Kerem Ben‐Meir, Yaron Meirow, Leonor Daniel, Guy Kariv, Mahdi Kurd, Michal Baniyash, Phenotypic Characterization and Isolation of Myeloid‐Derived Suppressor Cells, Current Protocols, 10.1002/cpz1.561, 2, 10, (2022).Wiley Online Library
21. Hadas Ashkenazi-Preiser, Or Reuven, Atara Uzan-Yulzari, Sharon Komisarov, Roy Cirkin, Sondra Turjeman, Carmel Even, Nira Twaik, Kerem Ben-Meir, Ivan Mikula, Leonor Cohen-Daniel, Yaron Meirow, Eli Pikarsky, Yoram Louzoun, Omry Koren, Michal Baniyash; The Cross-talk Between Intestinal Microbiota and MDSCs Fuels Colitis-associated Cancer Development. Cancer Research Communications 2 April 2024; 4 (4): 1063–1081.

• Prof. Michal Lotem, Hadasssah Medical Center. 
• Prof. Anahid Jewett, UCLA School of Dentistry and Medicine.
• Prof. Viktor Umansky, Deutsches Krebsforschungszentrum (DKFZ), Germany.
• Dr. Noam Levaot,  Ben Gurion Universiry of the Negev.
• Dr. Omri Koren, The Azrieli Faculty of Medicine Bar-Ilan University. 
• Dr. Michael Klutstein, Hadassah School Of Dental Medicine.

The research is supported by the Israel Science Foundation, the Israel Cancer Research Foundation, and the generous support of Dr. Matilda Beniyesh-Melnik.

We at the Baniyash lab are loving every activity involving food: have a picnic at the zoo, go for a brunch following pottery making, or just meet for a themed dinner at our PIs kitchen.