CELLULAR IMMmoLcx3~ 80, 187-197 (1983) Studies of the Thymus in Mice Bearing the Lewis Lung Carcinoma I. Thymic Natural Killer Cell Activity in 3LL Tumor-Bearing Mice’ DOMINIQUE KAISERLIAN,’ WILSON SAVINO, AND JEAN-FKANCOIS BACH INSERM U 25. Hspital Necker, 161, rue de Sbes. 75730 Paris Cedex 15, France Received March 1. 1983; acceptedApril 21, 1983 Natural killer (NK) cell activity of spleen and thymus was studied in Lewis lung carcinoma (3LL)bearing mice. A high level of hydrocortisone-sensitive NK cell cytotoxicity was found in the thymus after excision of the primary tumor, but not in nonamputated mice. Conversely, splenic NK cell activity was diminished in nonamputated tumor-bearing mice and remained unmodified in amputated tumor-bearing mice. Excision of the primary tumor prevented tumor- induced thymic atrophy and splenomegaly. Histological study of the thymus revealed the presence of metastatic cells within the cortex. These data suggest that NK cells or their precursors are present in the thymus and can be triggered or unmasked in situ by tumor cells migrating from the primary tumor. INTRODUCTION Nonspecific depression of the immune system has been reported in a variety of human cancers (l-3). In animals carrying experimental tumors, nonspecific immune suppression has been shown to affect mainly the T-cell compartment of the immune system, whereas thymus-independent responses were less affected (4, 5). Tumor cells seem to influence the immune system of the host by specific and nonspecific mech- anisms (6). With regard to suppressedimmune reactivity of the mice bearing Lewis lung car- cinoma (3LL) tumors, one possible explanation is a direct effect of the tumor itself on the immune system. Conversely, several studies have shown that suppressor T cells depressthe antitumor-specific response (7-l 1). In support of this, immunosup- pressive substancesor anti-host factors have been found in the sera of tumor-bearing mice (12-16). The evidence that naturally occurring cellular immune effector mechanisms play a biological role in the resistanceto tumor development and growth is mainly indirect (17). However, recent findings indicate that natural killer (NK) cells are involved in tumor rejection ( 18-20). It has recently been suggested that tumor cell metastases in lymphoid organs may alSect the immune statusof tumor-bearing mice (2 1). In addition, thymic atrophy has been demonstrated in tumor-bearing hosts (22). For these two reasonsit appeared of interest to study the NK activity of lymphoid cells from spleen ’ This work was supported by grants from the “Ligue Nationale contre le Cancer.” ’ To whom correspondence should be addressed. 187 0008-8749/83 $3.00 Copyright 0 1983 by Academic Press. Inc. All rights of reproduction in any form reserved.