Recent advances in the understating of tumor immunology suggest that cancer immunotherapy is an effective treatment against various types of cancer. In particular, the remarkable successes of immune checkpoint-blocking antibodies in clinical settings have encouraged researchers to focus on developing other various immunologic strategies to combat cancer. However, such immunotherapies still face difficulties in controlling malignancy in many patients due to the heterogeneity of both tumors and individual patients. Here, we discuss how tumor-intrinsic cues, tumor environmental metabolites, and host-derived immune cells might impact the efficacy and resistance often seen during immune checkpoint blockade treatment. Furthermore, we introduce biomarkers identified from human and mouse models that predict clinical benefits for immune checkpoint blockers in cancer.

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8 + T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro-and/or antitumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

Transforming growth factor beta 1 (TGF-β1) is an immunosuppresive cytokine that plays an essential role in immune homeostasis. It is well known that regulatory T (Treg) cells express TGF-β1; however, the role of autocrine TGF-β1 in the development, function, and stability of Treg cells remains poorly understood. We found that Treg cell-derived TGF-β1 was not required for the development of thymic Treg cells in mice, but played a role in the expression of latency-associated peptide and optimal suppression of naïve T cell proliferation in vitro. Moreover, the frequency of Treg cells was significantly reduced in the mesenteric lymph nodes of the Treg cell-specific TGF-β1-deficient mice, which was associated with increased frequency of IFN-γ-producers among Treg cells. TGF-β1-deficient Treg cells were more prone to express IFN-γ than TGF-β1-sufficient Treg cells in a dendritic cell-mediated stimulation in vitro as well as in an adoptive transfer study in vivo. Mechanistically, TGF-β1-deficient Treg cells expressed higher levels of Il12rb2 and were more sensitive to IL-12-induced conversion into IFN-γ-producing Treg cells or IFN-γ-producing exTreg cells than TGF-β1-sufficient Treg cells. Our findings demonstrate that autocrine TGF-β1 plays a critical role in the optimal suppressive activity and stability of Treg cells by downregulating IL-12R on Treg cells.

Methanol in aprotic solvents can serve as a case study for self-association via hydrogen-bonding, which is an important process in many biological and environmental systems. Incoherent broadband cavity-enhanced absorption spectroscopy (IBBCEAS), which provides enhanced sensitivity relative to conventional single-pass absorption techniques, has been used to characterize the third "free" O-H stretching overtone of methanol in four aprotic solvents (CCl4, CHCl3, CH2Cl2, and C6H6), including the transition wavenumber, bandwidth, and molar absorptivity. The absorption band characteristics indicate an increasing degree of nonspecific methanol-solvent interaction with increasing solvent dielectric constant, except in the case of benzene, which shows evidence of a specific, H-π interaction. Density functional theory with the polarizable continuum model was used to complement the results by assessing the accuracy of computational methods for calculating anharmonic O-H stretching frequencies. Finally, the self-association of methanol in these solvents at 298 K was also investigated using the concentration dependence of the overtone absorption intensity. The propensity for methanol's self-association in the solvents studied increases in the order: CH2Cl2 ∼ CHCl3 < C6H6 < CCl4.

GPCR-Gα protein–mediated signal transduction contributes to spatiotemporal interactions between immune cells to fine-tune and facilitate the process of inflammation and host protection. Beyond this, however, how Gα proteins contribute to the helper T cell subset differentiation and adaptive response have been underappreciated. Here, we found that Gα13 signaling in T cells plays a crucial role in inducing follicular helper T (Tfh) cell differentiation in vivo. T cell–specific Gα13-deficient mice have diminished Tfh cell responses in a cell-intrinsic manner in response to immunization, lymphocytic choriomeningitis virus infection, and allergen challenges. Moreover, Gα13-deficient Tfh cells express reduced levels of Bcl-6 and CXCR5 and are functionally impaired in their ability to adhere to and stimulate B cells. Mechanistically, Gα13-deficient Tfh cells harbor defective Rho-ROCK2 activation, and Rho agonist treatment recuperates Tfh cell differentiation and expression of Bcl-6 and CXCR5 in Tfh cells of T cell–specific Gα13-deficient mice. Conversely, ROCK inhibitor treatment hampers Tfh cell differentiation in wild-type mice. These findings unveil a crucial regulatory role of Gα13-Rho-ROCK axis in optimal Tfh cell differentiation and function, which might be a promising target for pharmacologic intervention in vaccine development as well as antibody-mediated immune disorders.