Thursday, November 23, 2017

Cancer-Immune Set Point


Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is required. Immunity is influenced by a complex set of tumour, host and environmental factors that govern the strength and timing of the anticancer response. Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy. In the context of the cancer-immunity cycle, such factors combine to represent the inherent immunological status - or 'cancer-immune set point' - of an individual.

It is always important to consider individual variation when judging therapeutic effectiveness or disease risk.  Different people have varying "immune profiles" - what the authors term the "cancer-immune set point" - and these different profiles will influence how each patient reacts to cancer immunotherapy.  Indeed, it is useful to speculate that these different set points affect how the patient's immune system reacts to a developing cancer in the first place - why in some individuals the early-stage cancer cells will be eliminated by the immune system and in other individuals the cancer cells are not recognized and grow to a full-fledged disease state.  Similarly, when you hear that "my grandfather smoked for 80 years and never got cancer and lived to be 96" or that "my grandma ate bacon-wrapped cheeseburgers three times a day for 70 years and died in her sleep at age 88" remember that there is individual variation and that we talk about disease risk - probabilities - not that lifestyle impacts disease to have a 100% deterministic effect on every person.  In like manner, immunotherapy may be generally effective, but it can not be expected to be equally effective for every individual.  Possibly, by understanding the mechanisms behind these differences, the effectiveness of immunotherapy can be enhanced even for relatively resistant individuals.

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