Clinical Cancer Research Vol. 12, 2049-2054, April 2006
© 2006 American Association for Cancer Research
Human Cancer Biology
Pediatric Cancers Are Infiltrated Predominantly by Macrophages and
Contain a Paucity of Dendritic Cells: a Major Nosologic Difference with
Adult Tumors
Jukka Vakkila1,2, Ronald Jaffe3, Marilyn Michelow3 and Michael T. Lotze1
http://clincancerres.aacrjournals.org/cgi/content/abstract/12/7/2049
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@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.