Nelson LaMarche, PhD

We are a cancer immunology lab in the Department of Pathology and the Cancer Biology Institute. Working closely with both physicians and basic scientists, we combine high-dimensional profiling of cancer patient tissues with detailed mechanistic studies in mouse models to develop new immunotherapies for solid tumors. While most cancer immunotherapies target T cells, our group primarily studies myeloid cells – monocytes, macrophages, granulocytes, and dendritic cells – which collectively often comprise up to 50% of total tumor cellularity. With the exception of dendritic cells, the majority of studies have demonstrated that myeloid cells promote cancer development through diverse mechanisms, in large part by suppressing the antitumor immune response. However, essentially all myeloid-directed immunotherapies have failed in clinical trials, largely because we lack an understanding of the main drivers of myeloid cell biology in tumors.

One defining feature of myeloid cells, and a central theme of our lab, is that most of these cells begin differentiation in the bone marrow in response to tumor cues, travel through the blood, and then complete their differentiation in the tumor. Throughout this entire cellular life cycle, myeloid cells receive signals that influence their differentiation trajectories and eventual functions within tumors. Therefore, the bone marrow and the tumor microenvironment represent distinct sites that can be targeted for myeloid-directed therapies in cancer and both of these organs must be studied simultaneously. We recently demonstrated that one pathway, the interleukin-4 (IL-4) signaling pathway, is highly upregulated in bone marrow during non-small cell lung cancer (NSCLC) development, drives the development of tumor-promoting myeloid cells, and can be therapeutically targeted in human cancer patients (LaMarche et al., 2023, Nature).

We integrate themes of metabolism, tissue immunology, and hematopoiesis into our research. Our studies emphasize the growing concept that cancer is a systemic disease, and we analyze how tumors alter normal organ physiology which, in turn, controls the antitumor immune response.