Tumor-specific responses in lymph nodes draining murine sarcomas are concentrated in cells expressing P-selectin binding sites

Tumor-draining lymph node (TDLN) cells develop substantial antitumor activi ty after activation on immobilized alpha CD3 and culture in low-dose IL-2. This study found that the minor subset of TDLN T cells expressing binding s ites for the adhesion receptor P-selectin (Plig(high) T cells) produced T l ymphoblasts with the most tumor-specific IFN-gamma synthesis in vitro and a ntitumor activity following adoptive transfer in vivo. The Plig(high) T cel ls constituted < 25 % of the cells with the phenotype of recently activated cells including high levels of CD69, CD44, or CD25, and low levels of CD62 L. The cultured Plig(high) TDLN were 10- to 20-fold more active against est ablished pulmonary micrometastases than cultured unfractionated TDLN, and > 30-fold more active than cultured TDLN cells depleted of the Plig(high) fr action before expansion (Plig(low) cells). Tumor-specific IFN-gamma synthes is in vitro paralleled the antitumor activities of the cultured fractions i n vivo, implying that increased Tc1 and Th1 effector functions contributed to the tumor suppression. Neither nonspecific interaction with the P-select in chimera used for sorting nor endogenous costimulatory activity in the Pl ig(high) fraction accounted for the marked increase in antitumor activities after culture. The cultured Plig(high) fraction contained a variety of pot ential effector cells; however, the CD8 and CD4 subsets of alpha beta T cel ls accounted for 95-97% of its antitumor activity. The authors propose that P-selectin sorting increased antitumor activities by concentrating Tc1 and Th1 pre-effector/effector cells before culture.