Mahata Group

Immune cell-mediated steroidogenesis

We discovered that immune cells can synthesise and secrete steroid hormones to regulate immune cell function. At present we know very little about the physiological and pathological role of this immune cell-mediated steroid biosynthesis. Therefore, we are curious to know the cause, mechanism and consequence of this immune cell steroidogenesis. We are committed to exploiting this knowledge to improve human health and combat disease.

Our initial studies suggest that immune cell-mediated steroid biosynthesis is involved in type-2 immune responses such as helminth infection, allergies and allergic asthma, pregnancy and many solid tumours. We hypothesise (1) immune cell steroidogenesis pathway is required to resolve immune response and restore tissue homeostasis in helminth infections (2) the pathway is mutated in allergies and allergic asthma, and (3) in solid tumours, steroid-producing immune cells are associated with anti-tumour immunosuppression and immune evasion.

We prioritised to study the role of steroidogenic immune cells in regulating anti-tumour immunity, and aim to develop a novel immunotherapeutic strategy against cancer. We undertake multidisciplinary approaches to answer our questions of why, how and when immune cells produce steroids.

Collaborators

Professor  Klaus Okkenhaug, University of Cambridge, UK

Professor Nicholas Coleman, University of Cambridge, UK

Professor Carlos Caldas, CRUK Cambridge Institute, UK

Professor Wiebke Arlt, University of Birmingham, UK

Dr Amit Roshan, CRUK Cambridge Institute, UK

Dr Amit Agrawal, Cambridge University Hospitals NHS Foundation Trust, UK

Dr Rahul Roychoudhuri, University of Cambridge, UK

Dr Simon Buczacki, University of Oxford, UK

Dr Abhik Mukhopadhyay, Cambridge Crystallographic Data Centre, UK

Dr Xiuwei Zhang, Georgia Institute of Technology, USA

Dr Mingfu Shao, Pennsylvania State University, USA

Key publications

1. Zhao, Q., Pramanik, J., Lu, Y., Homer, N. Z. M., Imianowski, C. J., Zhang, B., Iqbal, M., Shaji, S.K., Conway-Morris, A., Roychoudhuri, R., Okkenhaug, K., Qiu, P*. and Mahata, B*. (2025). Perturbing local steroidogenesis to improve breast cancer immunity. Nat Commun 16(1)3945.
    
2. Pramanik, J., Shaji, S. K., Zaman, M., Brown, B., Zhang, B., Yamashita-Kanemaru, Y., Okkenhaug, K., Roychoudhuri, R., Mukhopadhyay, A.*, and Mahata, B.* (2025). Drug repurposing study identified Posaconazole as an inducer of anti-tumour immunity. iScience 28(5)112488.
    
3. Sandor, L.F., Huh, J.B., Benko, P., Hiraga, T., Poliska, S., Dobo-Nagy, C., Simpson, J.P., Homer, N.Z.M., Mahata, B., and Gyori, D.S. (2024). De novo steroidogenesis in tumor cells drives bone metastasis and osteoclastogenesis. Cell Rep 43, 113936.
    
4. Sivakanthan, T., Tanner, J., Mahata, B., and Agrawal, A. (2024). Investigating the role of tumour-to-skin proximity in predicting nodal metastasis in breast cancer. Breast Cancer Res Treat 205, 109-116.
    
5. Roy, S., Roy, S., Mahata, B., Pramanik, J., Hennrich, M.L., Gavin, A.C., and Teichmann, S.A. (2023). CLICK-chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cells. Front Immunol 14, 1229703.
    
6. Roy, S., Sipthorp, J., Mahata, B., Pramanik, J., Hennrich, M.L., Gavin, A.C., Ley, S.V., and Teichmann, S.A. (2021). CLICK-enabledanalogues reveal pregnenolone interactomes in cancer and immune cells. iScience 24, 102485
    
7. Pramanik, J., Zhao, Q., Homer, N.Z.M., Kanemaru, Y., Hussein, H., Chakraborty, S., Roychoudhuri, R., Okkenhaug, K., and Mahata, B.* (2025) Primitive steroidogenesis in mast cells: A novel regulatory mechanism for mast cell function. (bioRxiv DOI: 10.1101/2025.02.05.636621)
    
8. Banik, D., Ward, C.J., Zhang, Z., Heraghty, D., Suresh, P., Li, B., Kedia, S., Davis, S., James Roy, J., Chapman, M., Mahata, B.*, and Klenerman, D.* (2024). Hyaluronidase unlocks sequestered CEACAM5 and improves CAR T-cell therapy in colorectal cancer. (bioRxiv DOI: 10.1101/2024.08.29.610222)
    
9. Ward, C.J., Chakraborty, S., Shaji, S.K., Veiga-Villauriz, C., Zhao, Q., Chen, X. and Mahata, B.* (2025) Glucocorticoid receptor and RUNX transcription factors cooperatively drive CD8 T cells dysfunction in human cancer. (bioRxiv DOI: 10.1101/2025.04.30.651472)
    
10. Hussein, H.A.M.*, Shaji, S.K., Veiga-Villauriz, C., Chakraborty, S., Pramanik, J., Ali, F.A.Z., Yuan, J., Khanfar, E., Makuyana, N., Ali, Y.M., Zhao, Q., and Mahata, B.* (2025) Immune cell de novo steroidogenesis regulates inflammation resolution and recovery in acute lung injury. (bioRxiv DOI: 10.1101/2025.08.29.673039)

*co-corresponding author

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Dr Bidesh Mahata

Research Group Leader
 

Group Members