Elements of cancer immunity and the cancer–immune set point

Daniel S. Chen & Ira Mellman

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Jan 18, 2017
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Nature 541, 321–330 (19 January 2017) doi:10.1038/nature21349

Received 23 August 2016 Accepted 11 November 2016 Published online 18 January 2017

Abstract

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.

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Figure 5: Factors that influence the cancer–immune set point

Figure 5: Factors that influence the cancer–immune set point

A map of cancer immunity showing the factors that affect the cancer–immune set point. The factors are placed on rings that denote their type, and each factor is also placed in the step of the cancer-immunity cycle in which they mainly act. For example, variations in HLA type reflect host genetics and are of greatest importance for T cell activation. Additional factors are being discovered rapidly. ARNTL, aryl hydrocarbon receptor nuclear translocator–like protein 1; ATG16L, autophagy-related protein 16; FcγRIII, Fc γ receptor III; HMGCR, HMG-CoA reductase; JAK/STAT, Janus kinase–signal transducers and activators of transcription; LOX, lysyl oxidase; NOD, nucleotide-binding oligomerization domain-containing protein; NSAIDs, non-steroidal anti-inflammatory drugs; RANKL; receptor activator of NF-κB ligand; ROS, reactive oxygen species.

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2 Comments

Go to the profile of Junyao Li
Junyao Li about 1 year ago

We are looking forward to see what happening on cancer immuno-prevention research studies, is there any progress so far?

Go to the profile of David Hicks
David Hicks 6 months ago

T cell activation starts during the pre or G1 phase of the cell cycle. The importance of understanding this event is embodied in the following hypothesis on the cause of cancer.

                                        THE INITIATING CAUSE OF CANCER, A HYPOTHESIS.

Cancer is a coalescence(1) of a chance mutation(2) and(3) a cellular specific(4) chronic(5) disease/injury(6) or mutation(7).

(1)  The mutation and the chronic effect must both act at the same time.

(2)  Chance mutations are known to randomly appear for no known reason. Environmental exposure can increase the risk of mutation. Chronic exposure, including smoking, can replace the role of chronic disease.

(3)  Neither a chance mutation nor a chronic disease/injury on their own, can cause cancer. A familial mutation will require a cellular specific injury.

(4)  Cell specificity, which is the cell type that initiates the chronic disease, dictates which cell type becomes cancerous.

(5)  Chronicity increases the possibility of the “chance” mutation by multiplying the possibility.

(6)  A chronic disease/injury in the alpha cell lineage, (from the endoderm); this will cover the majority of cancers; will have inhibited apoptosis or deleted p53 which then allows the chance mutation to survive. A chronic disease or injury in the beta cell lineage, (from the mesoderm), will have neither an inhibited or activated apoptosis, it will have an altered autophagy, which will also allow a mutation to survive. These chronic diseases can allow sporadic cancers to form. These actions can cause cancer if they are stalled in the pre-cell cycle pathways, or the G1 phase of the cell cycle.

(7)  A pre-mutated gene is required for genetic familial cancers. The mutation stalls pre-cell cycle pathways.

Note:  When a cancer cell metastasizes and travels elsewhere in the body, it does not pass on its “cancer” properties to other different types of cell. The stalled biological changes that occur in the initiating disease, such as growth factors, cytokines, T cell activation, etc. are spread throughout the body in the bloodstream. The combination of these changes is specific to the initiating cell type in the chronic disease, designed to allow only that type of cell to proliferate. So, if a prostate cancer cell metastasizes to bone, it does not cause bone cancer, it remains as prostate cancer, and is fed all the required biological changes required for prostate cell growth; through the blood stream.

                               Coalescence: To come together and form one whole.
 
Author:  David Hicks.                                Email: arose1800@hotmail.com