Density also matters in magnetic core memory (by J. McCranie, via Wikimedia Commons).Robust antitumor cytotoxic T lymphocyte responses are key to durable immunity. In-depth analysis of tumor-infiltrating T cells in cohorts of patients with two different epithelial cancers revealed that tumors dense with TILs were enriched in CD103+ tissue-resident T memory cells. These T cells exhibited enhanced proliferation and granzyme expression, and their numbers correlated with significantly reduced patient mortality.Ganesan A-P, …, Ottensmeier CH. Nat Immunol 2017 Jun 19; doi:10.1038/ni.3775.TCR predictions catching up to weather models (from National Centers for Environmental Prediction via Wikimedia Commons).Two papers in Nature devised methods to determine the T cells in a population that can bind a particular epitope. Analytical tools based on clustering were used to identify groups of sequences that shared core identities, which proved critical for successful antigen binding. The evolving algorithms may ultimately allow for development of a generalized model of TCR–pMHC recognition and help identify tumor-specific T cells based on detected TCR sequences.Dash P, …, Thomas PG. Nature 2017 Jun 21; doi:10.1038/nature22383.Glanville J, …, Davis MM. Nature 2017 Jun 21; doi:10.1038/nature22976.Finding the right tumor addresses with integrins (by Jordan via Pexels).Although many tumors overexpress the αV and α5 integrin subunits (bound to β subunits 1, 3, 5, or 6), functional interference has failed as an antitumor treatment. Instead, Kwan et al. targeted integrins with an RGD-binding moiety delivered with a fused Fc region. This reagent, in combination with a modified IL2 fusion that is long-lived, both engaged innate immunity and generated CD8+ T-cell immunity to three syngeneic murine tumors. Adding PD-1 blockade further enhanced the therapeutic activity.Kwan BH,…, Wittrup KD. J Exp Med 2017 June 5;214:1679–90.T cells see different epitopes on tumor proteins (by Hanabusa Itchō, via Wikimedia Commons).Vaccines comprising multiple neoantigens can be effective antitumor agents in mice. Such vaccines have now been tested in patients with advanced melanoma. Sahin et al. generated poly-epitope RNA-based vaccines, whereas Ott et al. used long peptides. Specific CD4+ and CD8+ T cells were induced that could kill autologous tumor cells, infiltrate tumors, and reduce recurrence and the frequency of metastasis. Administering anti–PD-1 was beneficial in patients whose cancer recurred after vaccination, providing support for the use of such combination therapy in patients.Sahin U, …, Türeci Ö. Nature 2017 Jul 5; doi:10.1038/nature23003.Ott PA, …, Wu CJ. Nature 2017 Jul 5; doi:10.1038/nature22991.Transferring epiphenomena (from Pixabay).Memory CD8+ T cells represent a diverse population composed of effector, central, and stem-like memory cells with distinct molecular programs regulated epigenetically. Homeostatic proliferation and self-renewal, as modeled by cytokine-driven proliferation in the absence of antigen, retains the effector memory program but induces differentiation of central and memory stem cells to effector memory cells, with associated reduction of self-renewal capacity and molecules that promote homing to lymph nodes.Abdelsamed HA,…, Youngblood B. J Exp Med 2017 June 5;214: 1679–1690.Stealing PD-1 antibodies (from VBC17 Victoria Graffiti via Flickr).Antibodies to PD-1 block interaction with PD-1 ligands, thereby preventing transmission of an inactivation signal to T cells. Within minutes, however, tumor-associated macrophages (TAMs) abscond with T cell–bound, but not soluble, antibody via TAM Fcγ receptors. Blocking these FcRs eliminated nonresponders and improved tumor regression.Arlauckas SP, …, Pittet MJ. Sci Transl Med 2017;9:eaal3604.