Interleukin-37 promotes colitis-associated carcinogenesis via SIGIRR-mediated cytotoxic T cells dysfunction

Interleukin-37b(hereafter called IL-37)was identified as fundamental inhibitor of natural and acquired immunity.The molecular mechanism and function of IL-37 in colorectal cancer(CRC)has been elusive.Here,we found that IL-37 transgenic(IL-37tg)mice were highly susceptible to colitis-associated colorectal cancer(CAC)and suffered from dramatically increased tumor burdens in colon.Nevertheless,IL-37 is dispensable for intestinal mutagenesis,and CRC cell proliferation,apoptosis,and migration.Notably,IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models.CD8^(+)T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice,enabling tumor evasion of immune surveillance.The dysfunction led by IL-37 antagonizes IL-18–induced proliferation and effector function of CD8+T cells,which was dependent on SIGIRR(single immunoglobulin interleukin-1 receptor-related protein).Finally,we observed that IL-37 levels were significantly increased in CRC patients,and positively correlated with serum CRC biomarker CEA levels,but negatively correlated with the CD8+T cell infiltration in CRC patients.Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancerimmunity cycle as therapeutic targets in CRC.

Utilizing Probabilistic Linear Equations in Cube Attacks

Cube attacks, proposed by Dinur and Shamir at EUROCRYPT 2009, have shown huge power against stream ciphers. In the original cube attacks, a linear system of secret key bits is exploited for key recovery attacks. However, we find a number of equations claimed linear in previous literature actually nonlinear and not fit into the theoretical framework of cube attacks. Moreover, cube attacks are hard to apply if linear equations are rare. Therefore, it is of significance to make use of probabilistic linear equations, namely nonlinear superpolys that can be approximated by linear expressions effectively. In this paper, we suggest a way to test out and utilize these probabilistic linear equations, thus extending cube attacks to a wider scope. Concretely, we employ the standard parameter estimation approach and the sequential probability ratio test （SPRT） for linearity test in the preprocessing phase, and use maximum likelihood decoding （MLD） for solving the probabilistic linear equations in the online phase. As an application, we exhibit our new attack against 672 rounds of Trivium and reduce the number of key bits to search by 7.