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.
Key publications
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1. Ward, C.J., Chakraborty, S., Shaji, S.K., Veiga-Villauriz, C., Al-deka, A., Zhao, Q., Pramanik, J., Chen, X. and Mahata, B.* (2025) Glucocorticoid receptor and RUNX transcription factors cooperatively drive CD8 T cells dysfunction in human cancer. Cell Reports 45 (5), 117367. (DOI: https: 10.1016/j.celrep.2026.117367)
2. Chakraborty, S., Pramanik, J., Alviter-Raymundo, G., Ward, C. J., Pramanik, J., Shaji, S.K., Yamashita-Kanemaru, Y., Ali, F. A. Z., Banik, D., Zhang, Z., Veiga-Villauriz, C., Homer, N.Z.M., Simpson, J., Laforest, S., Tong, S., Zhao, Q., Roy, J., Iqbal, M., Conway-Morris, A., Chapman, M., Roychoudhuri, R., Hussein, H., Klenerman, D., Saeb-Parsy, K. and Mahata, B.* (2026). Cortisol-resistant Chimeric Antigen Receptor (CAR)-NK cells overcome steroid-induced immunosuppression in lung cancer. Signal Transduction and Targeted Therapy 11 (1), 128. (DOI: 10.1038/s41392-026-02638-z)
3. Banik, D., Ward, C.J., Chakraborty, S., Zhang, Z., Heraghty, D., Suresh, P., Li, B., Kedia, S., Pramanik, J., Davis, S., James Roy, J., Chapman, M., Mahata, B.*, and Klenerman, D.* (2024). Enzymatic Remodelling of Tumour Microenvironment Enhances Anti-CEACAM5 CAR T-Cell Efficacy Against Colorectal Cancer. Advanced Science e09762 (DOI: 10.1002/advs.202509762)
4. 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. Nature Commuications 16(1)3945. (DOI:10.1038/s41467-025-59356-3)
5. 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. (DOI:10.1016/j.isci.2025.112488)
6. 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.
7. 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.
8. 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.
9. 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
10. Zhao, Q., Lu, Y., Shi, Z., Zhang, H., Shuen, L.C., Zhao, R., Ling, Y., Gao, Y., Zhang, Z., Sun, X., Qian, Y., Wang, X., Wang, C., Cong, B., Ni, X., Liu, Y., Zhao, M., Wang, Y., Mahata, B.*, and Qiu, P.* Spatio-temporal mapping of immune cell dynamics during human sequential lymph node metastasis. (bioRxiv DOI:10.64898/2026.03.17.712495)
11. 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)
12. 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)
13. Chakraborty, S., Pramanik, J., and Mahata, B.* (2021) Revisiting steroidogenesis and its role in immune regulation with the advanced tools and technologies. Genes & Immunity. 22(3):125-140.
14. Mahata, B.*, Pramanik, J., van der Weyden, L., Polanski, K., Kar, G., Riedel, A., Fonseca, N.A., Kundu, K., Campos, L.S., Ryder, E., Duddy, G., Walczak, I., Davidson, S., Okkenhaug, K., Adams, D.J., Shields, J.D.* and Teichmann, S.A.* (2020) Tumors induce de novo steroid biosynthesis in T cells to evade immunity. Nat Commun. 17;11(1):3588
15. Pramanik, J., Chen, X., Kar, G., Henriksson, J., Gomes, T., Park, J., Natarajan, K., Meyer, K.B., Miao, Z., McKenzie, A.N., Mahata, B.*, and Teichmann SA*. (2018) Genome-wide analyses reveal the IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation. Genome Medicine 10:76
16. Mahata, B.*, Zhang, X., Kolodziejczyk, A.A., Proserpio, V., Haim-Vilmovsky, L., Taylor, A.E., Hebenstreit, D., Dingler, F.A., Moignard, V., Göttgens, B., Arlt, W., McKenzie, A.N., Teichmann, S.A*. (2014) Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis. Cell Reports 7: 1130-1142.
*co-corresponding author
Dr Bidesh Mahata
Research Group Leader
Group Members