Description

High dimensional analysis of untreated early lung cancer lesions reveals novel myeloid immune responses to tumor

Yonit Lavin¹, Soma Kobayashi¹, Andrew Leader¹, El-Ad David Amir^1,2, Camille Bigenwald¹, Robert Sweeney¹, Romain Remark¹, Christian Becker¹, Naama Elephant³, Jacob Levine², Klaus Meinhof¹, Andrew Chow¹, Seunghee Kim-Shulze², Andrea Wolf¹, Emanuella Taioli¹, Raja Flores¹, Sacha Gnjatic¹, Adeeb Rahman¹, Dana Pe’er², Ido Amit³, Miriam Merad¹

¹Icahn School of Medicine at Mount Sinai, Oncological Sciences, New York, NY 10029, USA,

² Departments of Biological Sciences, Systems Biology and Computer Science, Columbia University, New York, NY, USA

³ Weizmann Institute of Science, Department of Immunology, Rehovot, Israel

Recently, monoclonal immunotherapy agents, particularly anti-PD-1 has demonstrated unprecedented clinical responses in patients with late stage and metastatic non-small cell lung carcinoma. These therapies target T cells, as they are the major effector cells in the tumor. These cells work in concert with innate cells which provide a first line of protection and are critical for antigen presentation. However, while many studies have focused on tumor infiltrating lymphocytes, little is known about the diversity of the myeloid repertoire at the tumor site. Work in our laboratory and others, have suggested that in various mouse tumor models, targeting specific cells of the myeloid compartment may increase response to immunotherapy and tumor regression. Therefore, understanding the composition of the myeloid compartment may be critical for developing new immunotherapy targets. Moreover, little is known about the nature of the immune response to early stage lung tumors.

To address this unmet need, we developed a multiscale immune profiling strategy to map the immune micro-environment of patient early lung adenocarcinoma lesions. We used high-dimensional analysis including mass-cytometry and multiplex-immunohistochemistry to map the immune microenvironment of 28 untreated lung adenocarcinoma. We demonstrate that early stage lung tumors have a robust immune response Utilizing a unique barcoding strategy that allows the simultaneous analyses of the tumor lesion, adjacent non-involved lung tissue and blood cells, we identified a response of both T cells and innate cells that was specific to the tumor. We propose that the tumor immune mapping helps stratify patients with early lung cancer lesions based on distinct immune patterns that will help tailor immunotherapy strategies and improve tumor responses.