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Imaging Mass Cytometry Reveals Tumor and Immune Spatial and Phenotypic Clusters Associated with Clinical Outcomes in Diffuse Large B Cell Lymphoma

105 Pages Posted: 7 Oct 2019 Publication Status: Review Complete

See all articles by Monirath Hav

Monirath Hav

Cedars Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute

Anthony Colombo

Cedars Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute

Erik Gerdtsson

University of Southern California - Department of Biological Sciences

Mohan Singh

University of Southern California - Department of Biological Sciences

Denaly Chen

University of Southern California - Department of Medicine

James Hicks

University of Southern California - Department of Biological Sciences

Peter Kuhn

University of Southern California - Department of Biological Sciences

Imran Siddiqi

University of Southern California - Department of Pathology

Akil Merchant

Cedars Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute

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Abstract

Multiplexed immune profiling of the tumor microenvironment (TME) in cancer has improved our understanding of cancer immunology, but complex spatial analyses of tumor immune interactions are lacking. Here we used imaging mass cytometry (IMC) to characterize the immunophenotypes and the spatial architecture in the TME of 33 cases of DLBCL. We develop the M-score, for identifying complex cellular phenotypes, and use this to identify a CCR4+Tim3+PDL1+ tumor phenotype that predicts outcomes better than the lymphoma international prognostic index (IPI). To characterize spatial interaction in the TME, we constructed spatial meta-clusters based on distances from CD8 T cells to other cells in the microenvironment. These clusters corresponded to micro-regions of immuno-suppression or immuno-activation, whose relative abundance correlated with clinical responses to chemotherapy. Finally, the CD8 spatial network alone could predict overall survival in lymphoma and point to a broader application of complex spatial analysis to gain functional insights into cancer immunology.

Keywords: tumor microenvironment, Non-Hodgkin Lymphoma, Image cytometry, Immunophenotyping

Suggested Citation

Hav, Monirath and Colombo, Anthony and Gerdtsson, Erik and Singh, Mohan and Chen, Denaly and Hicks, James and Kuhn, Peter and Siddiqi, Imran and Merchant, Akil, Imaging Mass Cytometry Reveals Tumor and Immune Spatial and Phenotypic Clusters Associated with Clinical Outcomes in Diffuse Large B Cell Lymphoma (October 3, 2019). Available at SSRN: https://ssrn.com/abstract=3464030 or http://dx.doi.org/10.2139/ssrn.3464030
This version of the paper has not been formally peer reviewed.

Monirath Hav

Cedars Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute ( email )

8700 Beverly Blvd.
Los Angeles, CA 90048
United States

Anthony Colombo

Cedars Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute

8700 Beverly Blvd.
Los Angeles, CA 90048
United States

Erik Gerdtsson

University of Southern California - Department of Biological Sciences

3616 Trousdale Parkway, AHF 107
Los Angeles, CA 90089-0371
United States

Mohan Singh

University of Southern California - Department of Biological Sciences

3616 Trousdale Parkway, AHF 107
Los Angeles, CA 90089-0371
United States

Denaly Chen

University of Southern California - Department of Medicine

United States

James Hicks

University of Southern California - Department of Biological Sciences

3616 Trousdale Parkway, AHF 107
Los Angeles, CA 90089-0371
United States

Peter Kuhn

University of Southern California - Department of Biological Sciences

3616 Trousdale Parkway, AHF 107
Los Angeles, CA 90089-0371
United States

Imran Siddiqi

University of Southern California - Department of Pathology

United States

Akil Merchant (Contact Author)

Cedars Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute

8700 Beverly Blvd.
Los Angeles, CA 90048
United States

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