Hello Isha Pandey

The immune system normally recognizes and eliminates abnormal cells, including cancer cells. Some immune cells, like T cells, can directly attack and destroy cancer cells. However, the immune system's ability to fight cancer cells depends on the cancer cells' ability to evade the immune response. If cancer cells can successfully evade immune surveillance and attack, they can proliferate and develop into a malignant tumor.

The cancer cells evolve mechanisms to evade the immune system. These mechanisms can include, losing molecules that make them visible to the immune system or producing molecules that suppress immune cell activity or modifying their microenvironment to make it hostile for the immune cells or even recruit certain immune cells that can dampen the immune response against cancer.

When cancer cells effectively evade the immune system, they can grow unchecked, leading to tumor formation and metastasis. So, it is the balance between the burden of cancer cells and the immune system's ability to fight them, and this depends on factors like tumor aggressiveness and the overall health of the immune system. As the cancer cells proliferate, they can develop a stronger resistance to immune attack, eventually overcoming the immune system's ability to control their growth.

Please note that the immune system does not ignore cancer cells. It actively tries to eliminate them. It is the cancer cells that develop strategies to evade immune detection and destruction, thereby allowing the growth of tumor.

Best,

Hello sir Malcolm Nobre

Thank you, that’s very well put. So it means some sub-immunogenic mutations or antigen presentation or local metabolic signals be shaping this threshold even before active immune suppression mechanisms evolve?

I wonder if this threshold is governed not just by the immune system’s capacity but also by how early tumor cells manipulate immune perception kind of like how chronic inflammation or persistent antigens lead to T cell exhaustion or tolerance in infections. Could a similar dynamic be at play in early tumor development?

Hello Isha Pandey,

There is a dynamic interplay between immunosurveillance and immune tolerance as far as cancer is concerned. The threshold is governed by tumor's characteristics, the host's immune status, and the tumor's ability to manipulate the immune environment.

Cancer can develop a state of immune tolerance by outmaneuvering the immune system's ability to control it.

Hello Isha Pandey,

Interesting question really. Did you come across any data that shows T cell exhaustion is more often seen in Chronic diseases in comparison to acute diseases ?

As far as I know, most immune evasion mechanism in cancer evolves similarly to how AMR bacteria evolves. That depends on the degree of mutation rate in that particular tissue, it's tropism, and also, as you said, the time it took to become more heterogeneous. The more heterogeneous a tumour cell becomes, both in its protein composition as well as DNA, the harder it is for our body it eliminate it.

Please share any article about T cell exhaustion in chronic diseases if you come across.

Regards,

Trishant Dinda

Dear Isha Pandey,

there is no any competiton between cancer and cell immune system. Cancer are percepted by a host as embrionic tissue, and lymphopoies support its unlimited growth as a highest priority. Thus, the physiological regeneration in normal tissues by young lymphocytes reduces dramatically, right up to accelerated host's death. Please, see all about in Google: researchgate an shoutko

Regards,

Aleksey N. Shoutko

Dear Dr. Shoutko,

Thank you very much for sharing this unique and provocative perspective. I hadnt previously encountered the idea of cancer being perceived by the host as embryonic tissue . It’s certainly a different way of thinking about tumor/immune system dynamics than the immune surveillance evasion framework I was initially exploring.

I appreciate your suggestion to read more about your work, and I’ll take a look at your ResearchGate publications to better understand your model in detail. If I may ask,how does your hypothesis account for clinical cases where immunotherapies (like checkpoint inhibitors) lead to tumor regression ? I am curious how those observations might be interpreted through the lens of your theory.

Thank you again for taking the time to share your insights.

Kind regards, Isha

Dear Dr. Trishant Dinda

Thank you so much for your thoughtful response. Your analogy between cancer immune evasion and antimicrobial resistance is very intriguing. It indeed aligns with the idea of evolutionary pressure shaping the heterogeneity and i mmune evasion capabilities of tumors.

I’ve reviewed few articles outlining how prolonged antigen exposure in chronic diseases drives Tcell exhaustion.

Article T cell exhaustion

Article CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer

Article Overcoming T cell exhaustion in infection and cancer

Dear Mrs. Isha,

all "therapeutic" remedies in convential therapy, including target' ones, are cytocidic/cytotoxic. There is no "tumor answer" without side effects. All side effects have manifested of injury of hematopoiesis , especialy its most sensitive lymphopoiesis lineage. The level of such injury is comparable with consequences of host's irradiation at dose 2-3 Gy. Thus, all THERAPIES of invasive cancer, apart surgery and hospis, based on total somatic poisoning/irradiation of the host, i.e. "tumor answere" arizes at the price of slow irreversible SOMATIC exhaustion, together with cancer. So, the "tumor' answer" is not more, than a byproduct of deadly "treatment" of the host, which breaks the natural trafic of mophpogenic stem/progenitors lymphocytes to the priviliged tumor and somatic tissues.

That is why, high % of 5-year survival for those 40 age old is doubtful achievement. Who will return them the lost -30-40 ys of natural lifespan?

Please, read my articles, for understanding. I'll be glad to disscus in a case of your disagreement, or detailes of "competitive" therapy proposed by me.

Warm regards,

prof. Aleksey N Shoutko