Mononuclear cell content of human solid tumors

Abstract

The mononuclear cell content and mononuclear cell function of human solid tumors were determined. Twenty-eight primary, and 17 metastatic solid tumors, including 6 lymph node metastases, were obtained from 45 patients. Cells were released from the tumors by mincing, scraping, and sieving. Analysis of the cellular content was determined by light microscopy, and tumor lymphocyte function was determined by stimulation of blastogenesis with PHA, PWM, Con-A, MLC, and SLO. A median of 3.3 X 10(7) tumor cells with 12.5% viability was obtained per gram of tumor, and a median of 7.8 X 10(6) lymphocytes with a viability of 96% and 0.35 X 10(6) macrophages with a viability of 85% was also obtained per gram of tumor. Significant lymphocyte responses to various mitogens and antigens were obtained in 31-40% of the tumor lymphocyte preparations. From 9.4% to 23% had vigorous responses with a stimulation index greater than 10. Primary tumors contained significantly more lymphocytes than metastatic tumors; thus, the percent lymphocytes in primary tumors was 13.5% compared to 5% for metastatic tumors. In contrast, some of the lymphocyte responses were significantly greater for metastatic tumors than primary tumors. These data suggest that the direct study of lymphocytes infiltrating primary and metastatic tumors may be a useful approach to understanding tumor immunity in man.

Bayesian cell-type deconvolution and gene expression inference reveals tumor-microenvironment interactions

“…During the past two decades numerous studies have revealed interactions between malignant cells and the stroma that promote diverse tumor functions including angiogenesis 4,5 , metastasis 6 , and immunosuppression 7,8 . Stromal cells differ between patients and tumor types [9][10][11][12][13][14][15] and the abundance of certain stromal cell populations are used in the clinic as biomarkers [16][17][18][19] and therapeutic targets [20][21][22][23][24][25] . These studies motivate direct measurements of cell types and the interactions between them in human subjects.…”

The Tumor Microenvironment: The Making of a Paradigm

“…Most of the early studies on the immune microenvironment of cancer focused on the characterization and functions of cellular and humoral immune components in the tumor microenvironment [11–36] These studies established that immunocytes including T cells [23, 32], B cells [14, 17], NK cells [24, 31] and macrophages [19, 20, 26, 27, 29, 33, 35, 36] have the capacity to infiltrate solid tumors in humans and in animals. Other studies demonstrated that immunoglobulins (Ig) and complement components could be detected in the microenvironment of solid tumors.…”

“…It was demonstrated that inflammatory cells (mainly macrophages) as well as proinflammatory molecules such as cytokines and chemokines whose physiologic function is to constitute a firewall against infectious agents, are causally involved in the initiation of certain types of cancer (inflammation-linked cancers) or in tumor progression of essentially all types of cancer [69, 70]. As mentioned above, several studies from the seventies of last century reported that mononuclear cells infiltrate solid tumors [19, 20, 26, 27, 29, 33, 35, 36]. It took several years to establish that such cells are heavily involved in the pro malignancy functions of cancer-linked inflammation [69–72].…”