T-CELLS FROM LATE TUMOR-BEARING MICE EXPRESS NORMAL LEVELS OF P56(LCK), P59(FYN), ZAP-70, AND CD3-ZETA DESPITE SUPPRESSED CYTOLYTIC ACTIVITY

Loss of T cell-associated signal transduction molecules has recently b een implicated in immune suppression in tumor-bearing hosts. In the pr esent study, we have examined this and related phenomenon extensively in a large number of tumor-bearing mice, analyzed individually. Spleni c T cells from tumor-bearing mice were isolated and characterized with respect to the following: (a) levels of three tyrosine kinases, p56(l ck), p59(fyn), and ZAP-70; (b) expression of CD3-zeta (c) alloreactive responses; and (d) antigen-specific responses. Contrary to recent rep orts, T cells from tumor-bearing mice were observed to express normal levels of lck, fyn, ZAP-70, and CD3-zeta Further, T cells showed healt hy alloreactive and antigen-specific responses until similar to 3 wk a fter post tumor challenge, when the tumors constituted similar to 20% of the body weight. Alterations with respect to some parameters were o bserved only in mice that had been bearing larger tumors for a conside rably longer period. As human tumors are unlikely to grow to such larg e sizes (e.g., > 20% of the total body weight), the significance of th e alterations in T cells expression of lck, fyn, ZAP-70, or CD3-zeta i n the immune status of cancer patients is unclear. Altogether, these r esults indicate that alterations in T cell signal transduction molecul es do not account for the profound tumor-specific suppression observed during tumor growth.