Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the breakdown of immune tolerance leading to excessive inflammation and tissue damage. Imbalance in the levels of cytokines represents one of the multifactorial causes of SLE pathogenesis and it contributes to disease severity. Deregulated levels of T helper type 1 (Th1), type 2 (Th2), and type 17 (Th17) cytokines have been associated with autoimmune inflammation. Growing evidence has shown deregulated levels of Th1, Th2, and Th17 cytokines in SLE patients compared to healthy controls associated with disease activity and severity. In this review, we describe and discuss the levels of Th1, Th2, and Th17 cytokines in SLE patients, and clinical trials involving Th1, Th2, and Th17 cytokines in SLE patients. In particular, with the exception of IL-2, IL-4, and TGF-β1, the levels of Th1, Th2, and Th17 cytokines are increased in SLE patients associated with disease severity. Current phase II or III studies involve therapeutic antibodies targeting IFN-α and type I IFN receptor, while low-dose IL-2 therapy is assessed in phase II clinical trials.

Psoriasis is an autoimmune disease mediated by disturbed T cells and other immune cells, and is defined by deep-red, well-demarcated skin lesions. Due to its varied etiologies and indefinite standard pathogenesis, it is challenging to consider the right treatment exclusively for each psoriasis patient; thus, researchers yearn to seek even more precise treatments other than topical treatment and systemic therapy. Using biologics to target specific immune components, such as upregulated cytokines secreted by activated immune cells, is the most advanced therapy for psoriasis to date. By inhibiting the appropriate pro-inflammatory cytokines, cellular signaling can be altered and, thus, can inhibit further downstream inflammatory pathways. Herein, the roles of cytokines with their mechanisms of action in progressing psoriasis and how the usage of biologics alleviates cellular inflammation are discussed. In addition, other potential pro-inflammatory cytokines, with their mechanism of action, are presented herein. The authors hope that this gathered information may benefit future research in expanding the discovery of targeted psoriasis therapy.

Germinal centers (GC) give rise to high-affinity and long-lived Abs and are critical in immunity and autoimmunity. IL-27 supports GCs by promoting survival and function of T follicular helper cells. We demonstrate that IL-27 also directly enhances GC B cell function. Exposure of naive human B cells to rIL-27 during in vitro activation enhanced their differentiation into CD20⁺CD38⁺CD27^lowCD95⁺CD10⁺ cells, consistent with the surface marker phenotype of GC B cells. This effect was inhibited by loss-of-function mutations in STAT1 but not STAT3. To extend these findings, we studied the in vivo effects of IL-27 signals to B cells in the GC-driven Roquin^san/san lupus mouse model. Il27ra^−/−Roquin^san/san mice exhibited significantly reduced GCs, IgG2a(c)⁺ autoantibodies, and nephritis. Mixed bone marrow chimeras confirmed that IL-27 acts through B cell– and CD4⁺ T cell–intrinsic mechanisms to support GCs and alter the production of pathogenic Ig isotypes. To our knowledge, our data provide the first evidence that IL-27 signals directly to B cells promote GCs and support the role of IL-27 in lupus.

Interleukin-27 (IL-27) is a pleiotropic cytokine but its immunosuppressive effects predominate during many in vivo immunological challenges. Despite this, evidence from tumor cell line transfer models suggested that IL-27 could promote immune responses in the tumor context. However, the role of IL-27 in immunity against tumors that develop in situ and in tumor immunosurveillance remain undefined. In this study, we demonstrate that tumor development and growth are accelerated in IL-27 receptor α (Il27ra)-deficient mice. Enhanced tumor growth in both carcinogen-induced fibrosarcoma and oncogene-driven mammary carcinoma was associated with decreased interferon-γ production by CD4 and CD8 T cells and increased numbers of regulatory T-cells (T_reg). This is the first study to show that IL-27 promotes protective immune responses against endogenous tumors, which is critical as the basis for future development of an IL-27 based therapeutic agent.

Antibody-drug conjugates (ADCs) are produced by integrating the specificity of monoclonal antibodies with cytotoxic payloads. ADCs are vital biologics for breast cancer treatment where they not only exert direct cytotoxicity but also promote anti-tumor immune responses against breast cancers. In this review, the structure, mechanism of action, and the anti-tumor immune response properties of approved and emerging ADCs are presented and discussed. The FDA-approved ADCs include trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG-Trop2), and trastuzumab deruxtecan (T-DXd), as well as two emerging ADCs, i.e. datopotamab deruxtecan (Dato-DXd) and ladiratuzumab vedotin (LV). Preclinical and clinical studies demonstrate their efficacy in multiple breast cancer subtypes (e.g. HER2⁺ and triple negative breast cancers). These ADCs exert anti-tumor activity through cytotoxic effects and immune responses primarily by recruiting and activating cytotoxic T cells. Moreover, combining ADCs with immune checkpoint inhibitors (ICIs) shows enhanced therapeutic outcomes. ADCs resistance is caused by heterogeneous target antigens expression, modified ADC processing including endocytosis and lysosomal trafficking, as well as upregulated drug-efflux pumps that decrease payload concentration intracellularly. Strategies to mitigate ADCs resistance include multi-target ADCs, and stability-enhancing linkers that also reduce off-target toxicities. ADCs continue to play key roles in breast cancer treatment, while next-generation ADCs may address current ADCs' limitations and resistance mechanisms.

Background: Psoriasis is a chronic inflammatory skin disease traditionally characterized by T cell-mediated immune responses. However, dendritic cells (DCs) and B cells also contribute to immune regulation in psoriasis. Their role in disease progression remains underexplored. Methods: This study utilized an imiquimod (IMQ)-induced psoriasis-like mouse model to investigate DC and B cell dynamics at different stages of disease progression (day 3, day 5 and day 7). Skin lesions were evaluated using the Psoriasis Area and Severity Index (PASI) and histological analysis. Flow cytometry was performed to assess the expression of CD11c ⁺ MHCII ⁺ DCs and CD19 ⁺ CD38 ⁺ B cells, while gene expression analysis using reverse transcriptase polymerase chain reaction (RT-PCR) of CD11c, H2-Aa, B cell activating factor (BAFF), interleukin (IL)-10, IL-6 and CXCR5 was conducted to elucidate immune modulation within the psoriasis skin microenvironment. Results: IMQ application induced progressive skin thickening, erythema and scaling, with PASI scores significantly increased at day 7 compared to controls ( p = 0.002), reflecting pronounced inflammation. Histological analysis revealed epidermal hyperplasia, hyperkeratosis and dermal immune cell infiltration. Skin CD11c ⁺ MHCII ⁺ DCs were significantly elevated at day 3 ( p < 0.01), corresponding with upregulation of CD11c and H2-Aa genes, while CD19 ⁺ CD38 ⁺ B cells expanded at later stages, peaking at day 7 ( p < 0.0001), associated with increased BAFF , IL-10 , IL-6 and CXCR5 expression. A reduction in circulating B cells was observed alongside increased skin infiltration, suggesting a possible redistribution associated with inflammation. Conclusion: Early DC activation corresponded with the initiation phase of inflammation, while the later expansion of B cells appeared to coincide with sustained inflammatory activity and disease progression. The coordinated presence of DCs and B cells in the skin microenvironment may influence disease severity and pathogenesis, which could provide fundamental insights for future investigations into potential therapeutic strategies.