HOW CANCER CELLS TO ESCAPE THE IMMUNE SYSTEM?

PRAGYA SANTRA, AMITY UNIVERSITY KOLKATA

The history of cancer research has always been a mystery in the result. Recently it was reported that cancer cells adapted themselves to grow and proliferate in an inflammatory environment. ENPP1, a readily accessible molecule found on the surface of cancer cells plays a major role in this mechanism. 

Naturally, free-floating DNA in the cytosol of the cancer cells triggers a red alert signifying the presence of unstable chromosomes. This cautious signal further activates a particular immunity pathway called the cGAS-STING pathway. cGAS binds to the chromosome and activates the immune response called STING which causes inflammation. Many cGAMP complexes also alert the neighboring immune cells in response to cancer. It has been noticed that in spite of self-destruction signals the cancer cells survived and thrive well in the unfavorable environment too. 

In a new study, the reason for such an exception is reported. The scientists could figure out the reason which permits the cancer cells to sustain even in an unsuitable environment. A new molecule is being found which destroys the warning signals before it reaches the immune cells for activation. Due to this reason, certain cancers do not respond to immunotherapeutic drugs. 

The current research highlights that the cancer cells counter the warning signals that activate the cGAS-STING complexes. ENPP1, a scissor-like protein coating the outer surface of the cancer cells foils the immune triggering signals, suppressing the innate immune response. When cGAMP departs the cell to reach its destination for triggering the neighboring immune cells ENPP1 digests it, hindering its function. Besides an immune-suppressing molecule, adenosine is also released which subdues the inflammation. Scientists observed that switching on ENPP1 suppresses the immune system and enhances metastasis.

The scientists are now in the process to develop drugs that can inhibit the ENPP1 on the cancer cells; which further can block the metastasis to some extent and support the immunotherapy. Simultaneously research is also in progress to prevent the over-production of immune-suppressive adenosine.

Also read:Climate Change and Animal Appearances: Renewed discussions on Gloger’s rule

Source: Metastasis and immune evasion from extracellular cGAMP hydrolysis; Jun Li, Mercedes A Duran et al.; American Association for Cancer Research; 2020-2021; doi: https://doi.org/10.1158/2159-8290.CD-20-0387 

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