Researchers at the Indian Institute of Science Uncover Key Insights to Boost Immunotherapy Effectiveness
Bengaluru, NFAPost: In a groundbreaking study published in Frontiers in Immunology, researchers at the Indian Institute of Science (IISc) have delved into the intricacies of cancer cell response to Interferon-gamma (IFN-γ) activation, shedding light on how certain non-responsive cancer cells can be manipulated to enhance the efficacy of immunotherapy.
Cancer immunotherapy, a revolutionary approach harnessing the body’s immune system to combat tumours, has emerged as a promising alternative to traditional treatments like chemotherapy and radiation. The focus has been on stimulating T cells through IFN-γ activation, a cytokine crucial for eliminating tumours efficiently and with fewer side effects.
Avik Chattopadhyay, a PhD student at the Department of Biochemistry, IISc, and the study’s first author, highlights the significance of IFN-γ: “Reports in the literature have shown earlier that if there are lower amounts of IFN-γ or defects in its signalling, then the tumours don’t respond well to the immunotherapy processes.”
The researchers found that only specific types of cancer cells respond optimally to IFN-γ activation, prompting them to investigate ways to make non-responsive cells more amenable to immunotherapy.
Upon treating cancer cells with IFN-γ, the team observed a change in the colour of the cell growth medium, indicating the release of acidic byproducts like lactic acid. Further exploration revealed that increased glycolysis, a process extracting energy from glucose, contributed to higher lactic acid production.
Distinct patterns emerged among cancer cell lines from different organs. Liver and kidney-derived cells exhibited increased production of nitric oxide (NO) and lactic acid upon IFN-γ activation, leading to the generation of toxic reactive oxygen species (ROS) and subsequent cancer cell death. In contrast, colon and skin-derived cells did not produce NO or lactic acid, suggesting poor responsiveness to immunotherapy.
To address this, the researchers explored methods to induce lactic acid and NO production in non-responsive cancer cells. Treatments involving potassium lactate and other molecules, surprisingly, resulted in a significant reduction in cancer cell growth.
Dipankar Nandi, Professor at the Department of Biochemistry, IISc, and corresponding author of the study, emphasizes that the findings are a proof-of-concept. He suggests further experiments in animal models to validate whether compounds targeting metabolism can enhance anti-tumour responses in hard-to-treat cancers in synergy with IFN-γ activation during immunotherapy.
The study, with its potential to revolutionize cancer treatment, marks a crucial step forward. As Nandi states, “The study is a proof-of-concept at this point.” The prospect of refining immunotherapy strategies offers hope for more effective and accessible cancer treatments in the future.
Reference:
Chattopadhyay A, Jagdish S, Karhale AK, Ramteke NS, Zaib A, Nandi D, IFN-γ lowers tumour growth by increasing glycolysis and lactate production in a nitric oxide-dependent manner: implications for cancer immunotherapy, Frontiers in Immunology (2023). DOI: 10.3389/fimmu.2023.1282653
Contact:
Avik Chattopadhyay
PhD student
Department of Biochemistry
Indian Institute of Science (IISc)
Email: [email protected]
Dipankar Nandi
Professor
Department of Biochemistry
Indian Institute of Science (IISc)
Email: [email protected]
Phone: 080-22933051
