A new strategy to strengthen cancer immunotherapy
Researchers from the Department of Pathology have developed an innovative approach to improve cancer immunotherapy by engineering immune cells that can resist the suppressive effects of cortisol—a natural steroid hormone found within many tumours.
The study, led by Soura Chakraborty and Bidesh Mahata and published in Signal Transduction and Targeted Therapy, reveals how lung tumours use cortisol to weaken the body's natural killer (NK) cells, preventing them from effectively attacking cancer.
Why cortisol matters
NK cells are a vital part of the immune system and can rapidly destroy cancer cells. However, the research showed that high levels of cortisol within the tumour microenvironment reduce NK cell activity, making it harder for the immune system to eliminate cancer.
The team discovered that cortisol not only suppresses the cancer-killing ability of NK cells but also increases cellular stress, creating another obstacle for effective immunotherapy.
Engineering stronger immune cells
To overcome this challenge, the researchers created cortisol-resistant CAR-NK cells. These genetically engineered immune cells can recognise cancer cells while remaining unaffected by the tumour's cortisol-rich environment.
In preclinical models of lung cancer metastasis, the modified CAR-NK cells controlled tumour growth significantly better than conventional CAR-NK cells, leading to a substantial reduction in tumour burden.
Paving the way for improved cancer treatments
The findings identify local cortisol signalling as a previously underappreciated barrier to successful immunotherapy in solid tumours. By removing this obstacle, cortisol-resistant CAR-NK cells could offer a promising new treatment strategy for lung cancer and other steroid-producing cancers.
The researchers believe this approach could also allow engineered immune cell therapies to be used alongside therapeutic steroids—medications commonly given to cancer patients—without compromising their anti-cancer effects, opening new possibilities for more effective and adaptable cancer immunotherapies.