June 12, 2024

Promoting the Efficacy of Immunotherapy in Non-Responsive Cancer Cells

A recent study conducted by researchers at the Indian Institute of Science (IISc) has shed light on ways to enhance the response of non-responsive cancer cells to immunotherapy. Immunotherapy is a treatment approach that harnesses the body’s immune system to target and eliminate cancer cells more effectively than traditional treatments such as chemotherapy or radiation.

The study focused on the role of Interferon-gamma (IFN-γ), a small signaling protein called a cytokine, in the activation of immune cells to target tumors. The researchers discovered that some types of cancer cells respond well to IFN-γ activation, while others do not. This finding highlights the need to develop strategies that can make non-responsive cancer cells more reactive to immunotherapy.

IFN-γ is produced by immune cells like T cells or natural killer cells and binds to tumors, inducing apoptosis or cell death. Previous studies have indicated that tumors with lower levels of IFN-γ or defects in its signaling pathway are less responsive to immunotherapy.

In the current study, when cancer cells were treated with IFN-γ in the lab, the researchers observed a change in the color of the cell growth medium to yellow, indicating the release of acidic byproducts like lactic acid. This led the team to investigate the role of these byproducts in cancer cell response.

The researchers found that increased production of lactic acid, as a result of enhanced glycolysis, occurred in liver and kidney cancer cell lines upon IFN-γ activation. This led to the production of toxic reactive oxygen species (ROS), causing oxidative damage and ultimately killing the cancer cells.

However, colon and skin cancer cell lines did not produce lactic acid or nitric oxide (NO) even after IFN-γ treatment, suggesting a poor response to immunotherapy.

To enhance the response of these non-responsive cancer cells, the researchers explored different approaches, including treating the cells with compounds like potassium lactate. Interestingly, these interventions significantly reduced the growth of the initially non-responsive cancer cells. This finding surprised the researchers because lactic acid is typically considered a metabolic dead-end product.

It is important to note that this study is still at the proof-of-concept stage. The researchers emphasize the need for further experiments in animal models to determine if compounds targeting metabolism can enhance the anti-tumor response in hard-to-treat cancers, particularly in combination with IFN-γ activation during immunotherapy.

These findings provide valuable insights into potential strategies for improving the effectiveness of immunotherapy in non-responsive cancer cells. By understanding the mechanisms behind the poor response and identifying ways to overcome these limitations, researchers can develop novel approaches that could offer new hope for patients with treatment-resistant cancers.


  1. Source: Coherent Market Insights, Public sources, Desk research
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