Immune checkpoint blockade (ICB) has revolutionized cancer care yet is ineffective in most patients. Predicting which patients will respond to ICB and how to enhance efficacy are major challenges. ICB efficacy is dependent on the presence of functional T cells in tumors, which are impacted by macrophages. We have discovered that lipid-laden macrophages (LLM) infiltrate ovarian tumors to promote cancer progression in association with immune evasion (Nat. Comm 2018). How LLMs accumulate lipids to impact ICB and whether they are predictive of ICB efficacy remain unexplored. Our objective is to determine how LLMs limit ICB and how this can be controlled via diet modulation. We hypothesize that LLM predict poor ICB response and that targeting LLM will enhance ICB efficacy. Our goals are to determine (i) the utility of LLM in predicting ICB efficacy and T cell dysfunction in patients; (ii) the origin and functional role of LLM in immunosuppression, hematopoiesis and ICB resistance; & (iii) how LLM and ICB are impacted by diet and obesity. We focus on tumors near lipid-rich adipose tissue, such as ovarian cancer (OC) which have high LLM and respond poorly to ICB.