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Blood Level of B and CD4+ Lymphocytes Measured before Induction of an Experimental Tumor in Rats Predicts Tumor Progression and Survival¹

Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, Georgia 30322 [M. K. D., Z-b. Z., J. M. W.], and University of North Texas, Health Science Center at Fort Worth, Department of Molecular Biology & Immunology, Fort Worth, Texas 76107 [R. H. G.]

After an initial series of experiments indicated that early responses of B lymphocytes were important in controlling tumor metastases in two rat models of cancer (N. Quan et al., Cancer Res., 59: 1080–1089, 1999), the present study assessed whether differences in the number of B lymphocytes that are normally present in different individual rats before any tumor development could predict tumor growth, metastases, and length of survival when tumor challenge subsequently occurred. Repeated baseline measures of several circulating lymphocyte subtypes (i.e., natural killer, B, CD4+, CD8+ lymphocytes) were made in individual inbred WAG rats before any introduction of tumor cells, and stable baselines for these subtypes were found. Animals were then injected with 2 x 10⁶ CC531 tumor cells (a syngeneic tumor) into the leg, and the size of the resulting primary tumor measured. Primary tumors were surgically removed 6–7 weeks after tumor-cell injection, and animals then followed until death from metastases. In two experiments, the size of the primary tumor as well as the length of time that animals survived correlated with the pretumor percentage of certain lymphocyte subtypes in peripheral blood before tumor-cell injection. Baseline percentage of B lymphocytes was significantly negatively correlated with the size of the primary tumor and was positively correlated with the duration of survival. Baseline percentage of CD4+ lymphocytes showed the opposite relationship, being positively correlated with tumor size and negatively correlated with survival time, although these correlations were lower than those for B lymphocytes. Percent B lymphocytes in circulation also declined during tumor development. In summary, a high percentage of endogenous peripheral blood B lymphocytes predicted growth of smaller primary tumors and longer survival after experimental tumor induction in a rat model, further suggesting that B lymphocytes are involved in protection against development of certain tumors.