Research led by the University of California San Francisco (UCSF) shows that dividing patients according to their individual immune profiles or ‘archetypes’ could result in better responses to cancer immunotherapy than current practice.
Immunotherapy has revolutionized the field of oncology, but it is more effective for some patients than others. “The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory,” Alexis Combes, UCSF researcher and first author of the study describing this work in Cell, told Inside Precision Medicine.
“Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic interventions in lung, kidney, or melanoma tumors. However, many more patients with the same tumor type have experienced minimal or no clinical benefit when provided the same treatment.”
To investigate the reasons behind this mixed treatment response, Combes and colleagues have set up the UCSF Immunoprofiler Initiative, a “translational platform to enhance treatment efficacy, develop precision medicines and understand the immunological basis for disease.”
In the current study, the researchers profiled 364 tumors from 12 different cancer types. From this they created an immune archetype for each patient. The immune archetype is determined by the cancer type, but also the tumor microenvironment and each patient’s immune system.
Overall, there were 12 different cancer archetypes ranging from ‘immune rich CD8 & macrophages’ to ‘myeloid centric dendritic cells 1’. These were not necessarily related to the type of cancer the patient had. This might mean that a melanoma tumor could actually be more similar to a lung tumor than another melanoma in terms of immune archetype.
“As opposed to focusing on the state of a single cell type, an immune system could be abstracted and conceived of by considering the prevalence of a collection of cells with linked states. The prototypical collections of these cells that define the system and its functional goals can then be considered an archetype of that response,” explained Combes.
“In other words, immune archetypes represent the limited number of immune states that is compatible with life that can be hijacked by cancers to hide from the immune system and slowly grow in patients.”
The researchers think their method of profiling tumors could help improve patient outcomes. “This new immune based classification scheme not only identifies which tumors are likely to be vulnerable to current immunotherapies, it also helps identify which patients might be most responsive in which clinical trial,” said Combes.
This research is still at the early stages, but provides a good first step towards improving outcomes by providing the 12 different archetypes.
“We are now working to expand this archetype analysis to the peripheral immune system, specifically to link tumor immune archetypes to specific collections of immune cell states in the blood,” explains Combes.
“This will not only reveal important biological associations between peripheral and tissue immune systems but could also be used to develop a clinical test for determining tumor archetype from a simple blood draw and theretofore facilitating patient stratification in the clinic.”
The research team are also working with other researchers at UCSF to define immune archetypes in patients undergoing immunotherapy and assess what impact different therapies have on tumors with different archetypes and evaluate how effective different therapies are on treating the different archetypes.