Cancer can progress rapidly and every minute lost in ineffective treatment increases the likelihood that the patient will die. Therefore, identifying patients most likely to respond to immunotherapy is an important challenge for our society.
With the advent of immunotherapy, cancer treatment has changed dramatically and some previously fatal cancers can now be cured. Unfortunately, not all patients respond to immunotherapy, so biomedical research is striving to understand (1) how to predict which patients will benefit and (2) how to sensitize more patients to treatment. In our team, we have identified a type of immune cell residing within tumors (macrophages) that favors the activation of another pathogenic cell type in tumors, fibroblasts. Our results suggest that as a result of this cellular interaction, immunotherapy in a very specific group of lung cancer patients becomes ineffective.
Our initial hypothesis is that disruption of this interaction between macrophages and fibroblasts will sensitize tumors to immunotherapy. To understand this cellular dialogue, we asked 3 questions: (1) Can the origin of macrophages predict which patients are most likely to benefit from immunotherapy? (2) How do macrophages and fibroblasts regulate each other and how can we interfere with this interaction to sensitize tumors to immunotherapy? (3) Can we modify the macrophage compartment to alter fibroblast permeability within tumors and promote anti-tumor T cell immunity?
We expect that the identification of pro-fibrotic mediators in macrophages will predict response to immunotherapy. We also anticipate that targeting this program will sensitize tumors to immunotherapy, opening up hopeful new therapeutic possibilities for lung cancer patients.
