For the immune system to respond appropriately, it must be able to identify what is abnormal. This process depends on antigen presentation - tumor derived proteins that are processed and presented to the immune cells in a specific way that allows for recognition. When the antigen presenting cells (APCs), like dendritic cells, are properly “loaded” or educated, they will “present” in a two-factor authorization response that serves to effectively show the Immune System what it need to recognize.
The Problem with Immune Recognition in Cancer
Tumors have multiple mechanisms that actually reduce their visibility to the immune system. They can down-regulate MHC expressions. They can impair antigen presentation and neo-antigen expression. They can even influence the terrain, or microenvironment, around itself. When this happens, it possible that the immune system is ‘working’ and activated - but it’s ‘blind’ to the tumor itself.
When tumors are characterized by low immune cell infiltration, low inflammatory signaling and minimal immune cell engagement, this is referred to as a ‘cold tumor’. Some targeted treatments, like checkpoint inhibitors, are less effective in this setting. They may be able to initiate an immune response, but there is no ‘target’.
This is where therapies that support antigen presentation become paramount. Double-loaded dendritic cell therapy (unique to Immunocine) is an example of this. The process by which dendritic cells are trained to the tumor is designed to improve proper and complete antigen presentation.
Recognition is the first step. Without this, activation is irrelevant.
If tumor antigens are not effectively presented, or if immune cells are not able to identify the target, increasing immune stimulation will not correct the problem. It will simply amplify a system that is not properly directed.
This distinction has direct implications for clinical decision-making. Before escalating therapy or layering additional immune-modulating agents, it is necessary to determine whether the immune system is engaged, suppressed, or unaware.
Subsequent interventions, no matter how targeted, are unlikely to produce a meaningful or sustained response.
Immunocine Cancer Center (as referenced in the article)
Double Loaded Dendritic Cell Therapy (IDCT).
Immunocine utilizes patient-specific dendritic cell–based immunotherapy designed to enhance antigen presentation, improve tumor visibility, and support targeted immune recognition within an individualized treatment framework.
Immunocine Website
References
Chen DS, Mellman I. Oncology Meets Immunology: The Cancer-Immunity Cycle. Immunity. 2013;39(1):1–10.
Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nature Immunology. 2013;14:1014–1022.
Beatty GL, Gladney WL. Immune escape mechanisms as a guide for cancer immunotherapy. Clinical Cancer Research. 2015;21(4):687–692.
Spranger S, Gajewski TF. Mechanisms of tumor cell–intrinsic immune evasion. Annual Review of Cancer Biology.
Binnewies M, Roberts EW, Kersten K, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nature Medicine. 2018;24:541–550.
1 comment
Thank you for this very important distinction on whether an immune system is functioning in such a way as to identify the ‘tumor’ and not simply been revved up without being aware of what the target is. I have observed inflammatory markers skyrocket when malutiple approaches to engage the immune system are utlitlzed and an unfavorable outcome of increased inflammatory markers, not decreased tumor activity is the outcome. Would love to leran more about how to determine when an immune system is aware of and engaged with addressing the tumor and how to support without driving inflammatory markers. Very much appreciate your work Dr. Maendel.