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Tumor-Specific Responses in Lymph Nodes Draining Murine Sarcomas Are Concentrated in Cells Expressing P-Selectin Binding Sites¹

Keishi Tanigawa^2,*,, Nobuhiro Takeshita^2,*,, Ronald A. Craig^2,*, Katie Phillips^*, Randall N. Knibbs^*, Alfred E. Chang and Lloyd M. Stoolman^3,*

Departments of ^* Pathology and Surgery, Division of Surgical Oncology, University of Michigan, Ann Arbor, MI 48109

Tumor-draining lymph node (TDLN) cells develop substantial antitumor activity after activation on immobilized CD3 and culture in low-dose IL-2. This study found that the minor subset of TDLN T cells expressing binding sites for the adhesion receptor P-selectin (Plig^high T cells) produced T lymphoblasts with the most tumor-specific IFN- synthesis in vitro and antitumor activity following adoptive transfer in vivo. The Plig^high T cells constituted <25% of the cells with the phenotype of recently activated cells including high levels of CD69, CD44, or CD25, and low levels of CD62L. The cultured Plig^high TDLN were 10- to 20-fold more active against established pulmonary micrometastases than cultured unfractionated TDLN, and >30-fold more active than cultured TDLN cells depleted of the Plig^high fraction before expansion (Plig^low cells). Tumor-specific IFN- synthesis in vitro paralleled the antitumor activities of the cultured fractions in vivo, implying that increased Tc1 and Th1 effector functions contributed to the tumor suppression. Neither nonspecific interaction with the P-selectin chimera used for sorting nor endogenous costimulatory activity in the Plig^high fraction accounted for the marked increase in antitumor activities after culture. The cultured Plig^high fraction contained a variety of potential effector cells; however, the CD8 and CD4 subsets of T cells 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.

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