Innate immunosurveillance against cancer

The success of checkpoint-blockade inhibitors, which relieve constraints on anti-tumor T cell responses, and the correlation of immunogenicity and patient survival with neo-antigen mutational load, have provided strong support for adaptive immune-surveillance against cancer in humans.  Whether the innate immune system can detect and remove transformed cells before their outgrowth into malignancy remains poorly defined.  Much of our understanding of the relationship between the immune system and cancer, in both mouse and human, comes from established tumors and shows tumor-supportive roles for inflammation and suppressed anti-tumor immunity.  Little research has focused on early phases of cancer.  Animal models that recapitulate cancer evolution from pre-malignancy to malignancy are limited.  Patients do not present until malignant disease is already established, thus human data relevant to immune regulation of pre-malignancy is lacking.  A new research direction in the lab is aimed at defining the innate immune barriers to cellular transformation during pre-malignancy.  We have generated several new mouse models for studying this problem.

We are recruiting students and post-docs to work on this problem using the novel mouse models we have created.  Please contact Dr. Blander if you are interested in taking a leadership position on this new and exciting work.

This work started with the finding that the innate immune system, specifically the inflammasome, can restrain stem cell proliferation and suppress the outgrowth of pre-cancer stem cells. Read more below:

Kent A, Yee Mon KJ, Hutchins Z, Putzel G, Zhigarev D, Grier A, Jia B, Kortlever RM, Barbet G, Evan GI, and Blander JM. A stromal inflammasome Ras safeguard against Myc-driven lymphomagenesis Nature Immunology (2025).
Innate immune barrier against oncogenic transformation Nature Immunology (2025).

Blander JM Macrophage barrier responses to oncogenic transformation Current Opinion in Immunology (2025).