Homing of CD8þ T lymphocytes to the tumor microenvironment is an important step for mounting a robust antitumor immune response. TGFb is responsible for CD103 (a E b 7 ) integrin induction in activated intraepithelial CD8 þ T lymphocytes. However, the interplay between TGFb and CD103 and their contribution to T-cell infiltration and antitumor activity remain unknown. Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Moreover, TGFb enhanced CD103-dependent Tcell adhesion and signaling, whereas it inhibited leukocyte function-associated antigen (LFA)-1 (a L b 2 ) integrin expression and LFA-1-mediated T-lymphocyte functions. Mechanistic investigations revealed that TGFb bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrinlinked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation, thereby initiating integrin insideout signaling. Collectively, our findings suggest that the abundance of TGFb in the tumor microenvironment may in fact engage with integrin signaling pathways to promote T-lymphocyte antitumor functions, with potential implications for T-cell-based immunotherapies for cancer. Cancer Res; 76(7); 1757-69. Ó2016 AACR.