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BackgroundThe signaling pathways involving phosphoinositide-3-kinases (PI3Ks) are highly conserved and tightly regulated to influence the activation, proliferation, and survival of all cell types. PI3K signaling plays a major role in T cell responses to antigen due to its position directly downstream of T cell receptor (TCR)/CD28 ligation.1 2 Our lab has recently shown that the cell surface protein TrIP (Transmembrane Inhibitor of PI3K, gene name: Pik3ip1) has a distinctly high expression on T cells and is capable of downregulating PI3K signaling in CD4+ T cells, acting as a negative regulator of T cell immune responses.3 4 These studies revealed that CD4+ T cells lacking TrIP expression exhibit a more Th1 inflammatory phenotype compared to WT T cells, both in vivo and in vitro.3 These data have led us to propose that TrIP restricts the inflammatory activity of T cells more generally, including CD8+ T cells, and that targeting/knockout of this negative regulator may promote anti-tumor immunity.MethodsUsing a conditional TrIP knockout mouse model developed in our lab, we have performed syngeneic tumor challenges in CD8+ T cell-specific TrIP knockout mice (TrIPfl/flE8icre). We have also characterized the tumor immune infiltrate of these mice to understand the impact of T cell-specific TrIP deficiency on the immune landscape.ResultsOur data thus far show that CD8+ T cell-specific TrIP knockout mice (TrIPfl/flE8icre) are resistant to growth of syngeneic tumors. In addition to increased tumor resistance, we have also found that tumors harvested from our TrIPfl/flE8icre knockout mice contain twice as many infiltrating T cells compared to their WT counterparts. We also found that CD8+ T cells appeared to be the main drivers of this increased T cell infiltration, as their frequency was double that of the CD4+ population in tumors transplanted into TrIP KO mice.ConclusionsWe describe data demonstrating that TrIP, a relatively novel PI3K inhibitor, plays a significant role in the antitumor immune activity of CD8+ T cells. Our that CD8+ T cell-specific TrIP knockout mice are resistant to tumor challenge and show more robust tumor CD8+ T cell infiltrate. With these data, we are excited to propose TrIP as a potential future immunotherapeutic target worthy of continued investigation.ReferencesOkkenhaug K, Turner M, Gold MR. PI3K signaling in B cell and T cell biology. Front Immunol 2014;5:557. doi:10.3389/fimmu.2014.00557Kane LP, Weiss A. The PI-3 kinase/Akt pathway and T cell activation: pleiotropic pathways downstream of PIP3. Immunol Rev 2003;192:7–20. doi:10.1034/j.1600-065X.2003.00008.xUche UU, Piccirillo AR, Kataoka S, et al. PIK3IP1/TrIP restricts activation of T cells through inhibition of PI3K/Akt. J Exp Med 2018;215:3165–3179. doi:10.1084/jem.20172018DeFrances MC, Debelius DR, Cheng J, Kane LP. Inhibition of T-cell activation by PIK3IP1. Eur J Immunol 2012;42:2754–2759. doi:10.1002/eji.201141653

Objectives Biologics are medication widely applied in management of inflammatory rheumatic diseases. The drugs were found to be effective but their application is associated with some disadvantages. Medication with biologics is relatively expensive, and in Poland, it is carried out in specialized centers. The study was designed to evaluate various aspects of satisfaction and dissatisfaction of the Polish patients treated with biologics. Methods Anonymous questionnaires were distributed in 23 Polish rheumatological centers involved in the treatment, 1231 questionnaires were used for analysis. Responses were received from 606 patients with rheumatoid arthritis (RA), 427 with ankylosing spondylitis (SA), 117 psoriatic arthritis (PS), and 62 adult patients with juvenile idiopathic arthritis (JIA) (in whom administration of the drugs had been introduced before they were 18-year-old), as well as 19 ones receiving the drugs due to other musculoskeletal disorders. The investigated group constituted about one-fifth of all rheumatic patients on biologics in Poland. Results The main reasons for satisfaction were positive influence of the treatment on family life (41% RA, 41% SA, 41% PS), general physical status (51% RA, 51% SA, very positive 43% PS), mental well-being (46% RA, 47% SA, 48% JIA, very positive 43% PS), sexual life (39% SA, 38% PS, 31% RA), sleep (39% RA, 41% SA, 36% PS, 40% JIA), in smaller part of the patients it had effect on working and financial situation. In general, satisfaction of the treatment was evaluated as positive or very positive in 84% patients with RA, 72% with SA, 87% with PS and 81% with JIA. In almost half of the patients, transportation to the medical center was a disadvantage of the treatment. 79% did not consider blood sampling as a problem for them. About one-third of the patients considered laboratory and imagine tests to be done before initiation of the medication as a difficulty, and for 27-47% waiting time for qualification for the medication was a significant disadvantage. The route of drug administration was without importance for 4/5 of the patients. Conclusions Summing up, the results were similar in the patients suffering from various diseases although those with PS felt the highest satisfaction (possible due to positive aesthetic effect), and those with SA had significant improvement in sexual life (probably due to younger age). Relatively low satisfaction was found in patients with JIA. There was low influence of medication on financial status of the patients however some of them returned to work. Application of biologics has low disadvantages and most of them are associated with organization of health services (waiting time for the tests, transportation to the medical centers). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3923