webpage_image.jpeg

Immune cell-mediated steroidogenesis

We discovered that immune cells, such as mast cells, basophils, T helper 2 cells and macrophages, synthesise and secrete steroid hormones that regulate immune cell function in context-dependent ways to restore homeostasis. This finding has opened an entirely new frontier in understanding how the balance between inflammation, immunity and homeostasis is controlled—with profound implications for cancer and inflammatory diseases. At present, we know little about the physiological and pathological role of this immune cell-mediated steroidogenesis (steroid biosynthesis). Therefore, we are curious to know the cause, mechanism and consequence of this fundamental biological process that evolved in early vertebrates and naturally selected. We are committed to exploiting this knowledge to improve human health and combat disease, particularly in cancer.

Our central research questions

Our lab operates at the intersection of three major challenges in medicine:

Aim 1: Breaking cancer's immune shield. Tumours have evolved a clever survival strategy—they hijack immune cells to produce steroids that suppress anti-tumour immunity. In other words, steroidogenic immune cells are maladapted in cancer to produce immunosuppressive steroids. We are developing strategies to block steroidogenic immune cells and unleash the body's natural cancer-fighting capacity. Early results from the lab show this approach can restore immune control of many solid tumours, particularly those cancers that induce this immunosuppressive pathway.

Aim 2: Preventing cancer before it starts. Chronic inflammation is a known culprit (enabler) in cancer development. We anticipate that by enhancing immune cell steroidogenesis, we can resolve inflammation appropriately in a more physiological way and prevent inflammation-driven cancers from taking hold. This preventive approach could transform how we identify and manage high-risk patients with chronic inflammatory conditions at risk of malignant transformation.

Aim 3: Patient stratification and precision diagnosis. Therapeutic success requires identifying patients who benefit from targeting immune cell steroidogenesis and steroid signalling. We aim to develop diagnostic tools and biomarkers to identify steroidogenic tumours and high-risk inflammatory states. This stratification will enable precision targeting of steroidogenesis-inhibiting therapies in cancer patients and steroidogenesis-enhancing strategies in patients with chronic inflammatory conditions predisposed to cancer.

Why our research matters

It's a fundamental biological process that evolved before glandular steroidogenesis, naturally selected to control inflammation and homeostasis, which is maladapted or dysfunctional in pathologies like cancer. It promises new therapies—immunotherapies and cell therapies—to overcome the immunosuppression in cancer.  Similarly, understanding how immune cell steroids resolve inflammation could lead to novel preventive strategies for patients at high risk of inflammation-driven cancers (such as those with inflammatory bowel disease, chronic hepatitis, or other inflammatory conditions).

Group members

Dr Hosni Hussein (Postdoctoral research associate): Investigating the role of immune cell steroidogenesis in regulation of inflammation and restoration of tissue homeostasis. Hosni obtained his PhD in Microbiology and Immunology (2018) from the East Carolina University, Greenville, NC, US. Before joining us, he worked at the Harvard Medical School, Massachusetts, USA as a postdoctoral researcher.

Miss Clara Veiga-Villauriz (PhD student): Investigating the role of extra-glandular steroidogenesis and steroid signalling  in cancer metastasis. Before joining us, she obtained her MSc in Integrated Immunology (2022) from the University of Oxford.

Mr Qiuchen Zhao (CRUK CC MRes/PhD  student): Investigating the role of immune cell-mediated steroidogenesis and steroid signalling in the tumour microenvironment of breast cancer and glioblastoma. Before joining us, he completed his Masters of Research (MRes) training from the Department of Oncology, University of Cambridge.

Mr Soura Chakraborty (Cambridge Trust International PhD student): Investigating the role and regulation of local steroidogenesis and steroid signalling in cancer inflammation and immunity. He is committed to determine the role of steroids signalling in NK cell function. Before joining us, he obtained his MSc in Biotechnology degree (2020) from the Jawaharlal Nehru University.

Dr Sanu K. Shaji (Postdoctoral research associate): Investigating the role of steroidogenic immune cells in the regulation of inflammation-driven cancer progression and targeting immune cell steroidogenesis pathway to reinstate anti-tumour immunity. Sanu did his PhD in Biotechnology (2021) from the School of Biotechnology, Amrita Vishwa Vidyapeetham, Kerala, India. Before joining us, he was a short-term postdoctoral fellow at the Norwich Medical School, University of East Anglia, Norwich, UK, supported by the University's Global Talent Search Fellowship.

Dr Jhuma Pramanik (Postdoctoral research associate): Investigating the regulation of immune cell-mediated steroidogenesis and its role in immune cell function. A major aim of her research is to determine the cell-intrinsic role of immune cell steroids.  She did her PhD (Biochemistry) from the Jadavpur University, Kolkata, India. Before joining Mahata lab, she worked with Dr Jon Audhya, University of UW-Madison (2008-2009), Dr Sarah Teichmann, Welcome Sanger Institute (2013-2018),  and Dr Virginia Pedicord, University of Cambridge (2018-2019) as a  postdoctoral research scientist. 

Mr Christopher Ward (PhD Student): Studying the role of glucocorticoid signalling in T lymphocytes function during anti-tumour immune responses, and exploiting that knowledge to develop novel therapeutic approaches (preclinical, experimental, proof of the principle studies) against cancer. Before joining us, he worked in the Buczacki Lab, Wellcome-MRC Cambridge Stem Cell Institute (now relocated to the Oxford University), and Clatworthy Lab, University of Cambridge. Chris obtained his M.Sc. & Diploma of Imperial College, Immunology from the Imperial College London (2016-2017).

Lab Alumni

Dr Rongrong Zhao (Clinician scientist, visiting, 2023): Investigated the role of immune cell steroidogenesis in cancer. At present, she is an oncologist and attending doctor at the Department of Medical Oncology, Shandong Cancer Hospital & Institute.

Dr Md Abdul Alim (SSMF Postdoctoral Research Fellow, 2024-2025): Investigated the role of steroid-producing mast cells in B16F10 lung metastasis. 

Mr Jack Chapman (Part II student, 2023): Investigated the role of StarD4 in regulating T helper (Th2) differentiation and Th2-mediated steroid biosynthesis.

Ms Ananyaa Jain (Part II Student, 2022): Investigated the role of StarD4 in the regulation of mitochondrial cholesterol import in T helper 2 lymphocytes.

Ms Megan Zaman (MPhil Student, 2021): Undertaking a structure-based drug-designing approach, she discovered new inhibitors of the immune cell steroidogenesis pathway.

Ms Beth Brown (Part II Student, 2021): Identified new inhibitors of CYP11A1 by virtual screening.

Collaborators

Professor Sir David Klenerman, University of Cambridge, UK

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

Professor William Griffiths, Swansea University, UK

Professor Ruth Andrew and Dr Natalie Homer, University of Edinburgh, 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 induzhcer 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)
11. Chakraborty S, Pramanik J, and Mahata B. (2021) Revisiting steroidogenesis and its role in immune regulation with the advanced tools and technologies. Genes & Immunity. https://doi.org/10.1038/s41435-021-00139-3
12.  Mahata B*, Pramanik J, van der Weyden L, Polanski K, Kar G, Riedel A, Fonseca NA, Kundu K, Campos LS, Ryder E, Duddy G, Walczak I, Davidson S, Okkenhaug K, Adams DJ, Shields JD* and Teichmann SA*. (2020) Tumors induce de novo steroid biosynthesis in T cells to evade immunity. Nature Communications https://www.nature.com/articles/s41467-020-17339-6
13. Pramanik J, Chen X, Kar G, Henriksson J, Gomes T, Park J, Natarajan K, Meyer KB, Miao Z, McKenzie AN, 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
14. Mahata B*, Zhang X, Kolodziejczyk AA, Proserpio V, Haim-Vilmovsky L, Taylor AE, Hebenstreit D, Dingler FA, Moignard V, Göttgens B, Arlt W, McKenzie AN, Teichmann SA*. (2014) Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis. Cell Reports 7: 1130-1142. 

*corresponding/co-corresponding author