lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

Human Keratinocyte Carcinomas Have Distinct Differences in Their Tumor-Associated Macrophages

22 Pages Posted: 18 Nov 2018

See all articles by Xiaodong Jiang

Xiaodong Jiang

Yale University, School of Medicine, Department of Dermatology

Nika Cyrus

Yale University, School of Medicine, Department of Dermatology

Diana A. Yanez

Yale University, School of Medicine, Department of Dermatology; Yale University, School of Medicine, Department of Pathology

Richard K. Lacher

Yale University, School of Medicine, Department of Dermatology

Anne Marie Rhebergen

Yale University, School of Medicine, Department of Dermatology

Carolyn Brokowski

Yale University, School of Medicine, Department of Dermatology

Anjela Galan

Yale University, School of Medicine, Department of Dermatology; Yale University, School of Medicine, Department of Pathology

Samuel Book

Yale University, School of Medicine, Department of Dermatology

Oscar Colegio

Yale University, School of Medicine, Department of Dermatology; Yale University, School of Medicine, Department of Pathology; Yale University, School of Medicine, Yale New Haven Transplantation Center; Yale University, School of Medicine, Yale Cancer Center

More...

Abstract

Despite both being keratinocyte carcinomas mainly caused by ultraviolet radiation, cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) have different clinical behaviors. Whether these distinct features are associated with tumor-associated macrophages (TAMs) is largely unknown. The main goal of this study was to conduct a comprehensive analysis of density and polarization states of TAMs in SCCs versus BCCs. The role of lactic acid in TAM polarization in SCC versus BCC was examined. We found that SCCs have a higher density of CD68 TAMs compared to BCCs. TAMs in SCCs express higher levels of TAM-associated markers (arginase-1, MMP9, CD40 and CD127) than those in BCCs. Interestingly, differential expression of TAM-associated markers between SCCs and BCCs was reproduced in human monocytic THP-1 cells stimulated with SCC- or BCC-conditioned media. Analysis of soluble factor(s) in these tumors further revealed that SCCs have a significantly higher concentration of lactic acid than BCCs, and lactic acid was sufficient to upregulate TAM markers. Our results demonstrate that TAMs in SCCs versus BCCs differ in density and polarization states, which can be determined by soluble factors including tumor-derived lactic acid. These differences in TAMs may contribute to the distinct clinical behaviors of SCCs versus BCCs.

Funding Statement: This work was supported by grants from NIH (5K08CA172580), Doris Duke Charitable Foundation (15-007374), and NIH Medical Scientist Training Program (T32 GM007205).

Declaration of Interests: Authors report no conflicts of interest.

Ethics Approval Statement: De-identified, discarded tissue was obtained consistent with the general requirements of the protocol approved by the Yale Human Investigations Committee (HIC#200002048).

Keywords: Tumor-Associated Macrophages, TAMs; Squamous Cell Carcinoma, SCC; Basal Cell Carcinoma, BCC; Macrophage Polarization and Density; Lactic Acid

Suggested Citation

Jiang, Xiaodong and Cyrus, Nika and Yanez, Diana A. and Lacher, Richard K. and Rhebergen, Anne Marie and Brokowski, Carolyn and Galan, Anjela and Book, Samuel and Colegio, Oscar, Human Keratinocyte Carcinomas Have Distinct Differences in Their Tumor-Associated Macrophages (November 16, 2018). Available at SSRN: https://ssrn.com/abstract=3286114

Xiaodong Jiang

Yale University, School of Medicine, Department of Dermatology ( email )

333 Cedar Street
New Haven, CT 06520-8034
United States

Nika Cyrus

Yale University, School of Medicine, Department of Dermatology

333 Cedar Street
New Haven, CT 06520-8034
United States

Diana A. Yanez

Yale University, School of Medicine, Department of Dermatology

333 Cedar Street
New Haven, CT 06520-8034
United States

Yale University, School of Medicine, Department of Pathology

310 Cedar Street LH 108
PO Box 208023
New Haven, CT 06520
United States

Richard K. Lacher

Yale University, School of Medicine, Department of Dermatology

333 Cedar Street
New Haven, CT 06520-8034
United States

Anne Marie Rhebergen

Yale University, School of Medicine, Department of Dermatology

333 Cedar Street
New Haven, CT 06520-8034
United States

Carolyn Brokowski

Yale University, School of Medicine, Department of Dermatology ( email )

333 Cedar Street
New Haven, CT 06520-8034
United States

Anjela Galan

Yale University, School of Medicine, Department of Dermatology ( email )

333 Cedar Street
New Haven, CT 06520-8034
United States

Yale University, School of Medicine, Department of Pathology ( email )

310 Cedar Street LH 108
PO Box 208023
New Haven, CT 06520
United States

Samuel Book

Yale University, School of Medicine, Department of Dermatology

333 Cedar Street
New Haven, CT 06520-8034
United States

Oscar Colegio (Contact Author)

Yale University, School of Medicine, Department of Dermatology ( email )

333 Cedar Street
New Haven, CT 06520-8034
United States

Yale University, School of Medicine, Department of Pathology ( email )

310 Cedar Street LH 108
PO Box 208023
New Haven, CT 06520
United States

Yale University, School of Medicine, Yale New Haven Transplantation Center ( email )

333 Cedar Street
New Haven, CT 06520-8034
United States

Yale University, School of Medicine, Yale Cancer Center ( email )

333 Cedar Street
New Haven, CT 06520-8034
United States

Click here to go to TheLancet.com

Go to TheLancet.com

Paper statistics

Abstract Views
82
Downloads
4