Limitations include IL-4 expression may not directly correlate with a dupilumab-treatment phenotype, and a focus on a single cytokine rather than multiple genes, which was beyond the scope of this study. The in-silico analysis is an important proxy that contributes to our knowledge of oncologic safety of the IL-4 biologic medication class.

Both anti-CD74/anti-CD20 and anti-IL4R/anti-CD20 were able to mediate ADCC and ADCP, but CD74-targeting therapeutic antibodies could also mediate direct cytotoxicity. Overall, this study strongly indicates that development of bispecific antibodies that target multiple B cell receptors expressed by lymphoma could provide improved defense against relapse and rituximab resistance.

Because the evidence is modest, the question remains open as to whether dupilumab can be safely combined with other monoclonal antibodies. Dupilumab does not exert immunosuppressive effects and does not impair the activity of cytochrome P450 isozymes.

In terms of mechanism, we found that the inhibition of sphingomyelin synthase 2 could downregulate the expression of IL4Rα and CSF1R, thereby attenuating M2 polarization. The sphingomyelin synthase 2 inhibitor YE2 or sphingomyelin synthase 2 deficiency can prevent macrophage M2 polarization in pancreatic cancer, and sphingomyelin synthase 2 could be a new potential target for the treatment of pancreatic cancer.

In the case of STAT1, CASP3, PARP1, and PRKDC proteins, a transient increase in their content was observed at early time points (3-12 h) after the ATRA treatment. Obtained data on nuclear proteome composition and dynamics during granulocytic differentiation could be beneficial for the development of new treatment approaches for leukemias with the mutated p53 gene.

Regarding patients with breast cancer, we found the following: Asperolide A could be another curative drug; targeting transforming growth factor-beta (TGFβ) and bone morphogenetic protein (BMP) signaling pathways, along with osteoclast activity, could be a favorable therapeutic approach in the preclusion of osteolytic bone destruction; TRAF6 inhibitors such as 6877002 appear promising; aiming the BMP4-SMAD7 signaling axis is an innovative therapeutic approach; there is favorable proof for the plausible therapeutic utilization of bone aiming immunostimulatory MOF (BT-isMOF) nanoparticles, and inhibition of IL4R and macrophages could have therapeutic benefits. For lung cancer, the function of LIGHT in osteolytic osseous illness instigated by metastatic non-small cell lung cancer should be highlighted.

There is only one FDA-approved therapy of myeloid cancers, gemtuzumab ozogamicin (Myelotarg) for AML approved > 10 years ago...So, will immune therapy cure AML? Stand by.

Despite having some features that are less common in DLBCL (MAL and CD23 expression, JAK-STAT activation), these tFL-PMBLsig-pos cases lack the most characteristic CN alteration seen in PMBL (9p24.1 gain/amplification). This cohort expands the biologic heterogeneity of tFL, illustrating a subset with gene expression and some genetic features reminiscent of PMBL, with potential treatment implications that include the use of novel targeted therapies.

Finally, the Kaplan-Meier analysis established the prognostic association of the key DEGs, in CaCx cohort. The STAT3 and associated key genes discovered from our study establish a strong pathogenic role of JAK/STAT3 pathway in HPV-mediated cervical carcinogenesis.

Analysis of The Cancer Genome Atlas database identified several tumor indications in which high expression of a macrophage-STAT6 signature correlates with poor survival, including HCC, stomach, and bladder cancer (p=0.012, p=0.00056, and p=0.0021, respectively). Conclusions In summary, we demonstrated that exoASO-STAT6 has a durable PK/PD profile in the liver of preclinical species, identified PD biomarkers with good clinical translational potential and described a rationale for selecting cancer subtypes that could benefit from treatment with exoASO-STAT6.

Our results proved that targeting EGFR T790M-cis-L792F/STAT3 Tyr705/IL-4 pathway could be a potential strategy to suppress osimertinib resistance in NSCLC.