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Pediatric Cancers Are Infiltrated Predominantly by Macrophages and Contain a Paucity of Dendritic Cells: a Major Nosologic Difference with Adult Tumors

Authors' Affiliations: ¹ Molecular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; ² Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland; and ³ Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Requests for reprints: Jukka Vakkila, Department of Bacteriology and Immunology, Haartman Institute, Haartmaninkatu 31, FIN-00014 University of Helsinki, Helsinki, Finland. Phone: 358-40-821-6939; Fax: 358-10-414-4619; E-mail: jukka.vakkila{at}mehilainen.fi.

Purpose: Adult cancer is frequently preceded by a period of prolonged chronic inflammation caused by infectious microbial agents or physical or chemical irritants. By contrast, an association between the classic pediatric neoplasias and inflammatory triggers is only rarely recognized. We hypothesized that the difference could be reflected in the inflammatory cell infiltrates of pediatric and adult cancer.

Experimental Design: Three investigators retrospectively studied 27 pediatric and 13 adult cancers at first diagnosis by immunohistochemistry. Inflammatory cells were identified and counted, and their location in relation to tumor tissue was analyzed.

Results: A majority of tumor-associated leukocytes (TAL) in adult tumors were located at the edges of tumor islands forming inflammatory foci between the supporting stroma and the malignant infiltrate. In contrast, TALs in pediatric tumors were scattered within the malignant tumor islands. In adult tumors, TALs were composed of diverse leukocyte types; but in pediatric tumors, the infiltrating cells were predominantly macrophages that accumulated in areas of necrosis within the tumors. The most striking feature in the pediatric tumors was the virtual absence of dendritic cells. The proportion of intratumoral dendritic cells in pediatric samples was 4.1%; whereas in adult tumors, they formed 36.9% of TALs within the tumor islands and 25.1% around the tumors.

Conclusions: We conclude that TALs in pediatric cancers are composed mainly of macrophages and largely devoid of dendritic cell. The findings may provide a major nosologic difference reclassifying pediatric and adult tumors based on nominal inflammatory and noninflammatory etiologies.