Active, specific immunotherapy for lung cancer: hurdles and strategies using genetic modification  Robert J Korst, MD, Ronald G Crystal, MD  The Annals of Thoracic Surgery  Volume 76, Issue 4, Pages 1319-1326 (October 2003) DOI: 10.1016/S0003-4975(03)00651-9

Fig 1 Cellular anti-tumor immunity. Tumor cells present tumor-associated antigens (TAAs) to naive CD8+ T lymphocytes in the context of the major histocompatability complex (MHC) class I molecules. In the presence of either co-stimulation (B7.1/B7.2) from activated antigen-presenting cells (APCs) or cytokine “help” (interleukin-12) from activated CD4+ T cells, these CD8+ cells become activated, TAA-specific cytotoxic T lymphocytes (CTLs). In the absence of co-stimulation and cytokines, anergy (tolerance) is thought to occur. CD4+ T cells become activated when soluble TAAs, which have been engulfed and processed by naive APCs, are presented to naive CD4+ cells through MHC class II (with B7 co-stimulation). Another pathway for CTL activation involves “crosspriming” by APCs, in which processed TAAs are presented to naive CD8+ cells using MHC class I. In this scenario cytokine help for CD4+ cells is not needed, because the activated APCs possess the necessary co-stimulatory molecules. CD40/CD40 ligand interactions further activate APCs to allow more efficient TAA presentation. Activated CTLs proliferate and migrate to tumors, bind to tumor cells through MHC class I, and induce apoptosis of the target tumor cell through several potential mechanisms (perforin, Fas ligand). The Annals of Thoracic Surgery 2003 76, 1319-1326DOI: (10.1016/S0003-4975(03)00651-9)