Understanding the modulation of specific immune cells within the tumor microenvironment (TME) offers new hope in cancer treatments, especially in cancer immunotherapies. In recent years, immune modulation and resistance to immunotherapy have become critical challenges in cancer treatments. However, novel strategies for immune modulation have emerged as promising approaches for oncology due to the vital roles of the immunomodulators in regulating tumor progression and metastasis and modulating immunological responses to standard of care in cancer treatments. With the progress in immuno-oncology, a growing number of novel immunomodulators and mechanisms are being uncovered, offering the potential for enhanced clinical immunotherapy in the near future. Thus, gaining a comprehensive understanding of the broader context is essential. Herein, we particularly summarize the paradoxical role of tumor-related immune cells, focusing on how targeted immune cells and their actions are modulated by immunotherapies to overcome immunotherapeutic resistance in tumor cells. We also highlight the molecular mechanisms employed by tumors to evade the long-term effects of immunotherapeutic agents, rendering them ineffective.

Cancer-associated thrombosis is the second-leading cause of mortality in patients with cancer and presents a poor prognosis, with a lack of effective treatment strategies. NAD(P)H quinone oxidoreductase 1 (NQO1) increases the cellular nicotinamide adenine dinucleotide (NAD⁺) levels by accelerating the oxidation of NADH to NAD⁺, thus playing important roles in cellular homeostasis, energy metabolism, and inflammatory responses. Using a murine orthotopic 4T1 breast cancer model, in which multiple thrombi are generated in the lungs at the late stage of cancer development, we investigated the effects of regulating the cellular NAD⁺ levels on cancer-associated thrombosis. In this study, we show that dunnione (a strong substrate of NQO1) attenuates the prothrombotic state and lung thrombosis in tumor-bearing mice by inhibiting the expression of tissue factor and formation of neutrophil extracellular traps (NETs). Dunnione increases the cellular NAD⁺ levels in lung tissues of tumor-bearing mice to restore the declining sirtuin 1 (SIRT1) activity, thus deacetylating nuclear factor-kappa B (NF-κB) and preventing the overexpression of tissue factor in bronchial epithelial and vascular endothelial cells. In addition, we demonstrated that dunnione abolishes the ability of neutrophils to generate NETs by suppressing histone acetylation and NADPH oxidase (NOX) activity. Overall, our results reveal that the regulation of cellular NAD⁺ levels by pharmacological agents may inhibit pulmonary embolism in tumor-bearing mice, which may potentially be used as a viable therapeutic approach for the treatment of cancer-associated thrombosis.

Background: Dunnione has anti-inflammatory properties arising from its ability to alter the ratio of NAD⁺/NADH through NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action, followed by subsequent inhibition of NF-κB and inflammatory cytokines. Psoriasis is a chronic, inflammatory skin disorder in which the IL-23/Th17 axis plays an important role in inflammation. However, it is unclear whether modulation of NAD⁺ levels affects psoriasis, such as skin inflammation. Therefore, in this study, we investigated the effect of NAD⁺/NADH ratio modulation on imiquimod (IMQ)-induced, psoriasis-like skin inflammation in mice. Methods: Psoriasis-like skin inflammation was generated by daily topical application of IMQ cream. The severity of dermatitis was assessed using the Psoriasis Area Severity Index (PASI) and histochemistry. Expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay and quantitative PCR. Acetylation of NF-κB p65 and STAT3 was determined by Western blotting. Results: Dunnione improved IMQ-induced epidermal hyperplasia and inflammation, consistent with decreased levels of inflammatory cytokines (IL-17, IL-22, and IL-23) in skin lesions. Moreover, we found that an increase in the NAD⁺/NADH ratio by dunnione restored SIRT1 activity, thereby reduced imiquimod-induced STAT3 acetylation, which modulates the expression of psoriasis-promoting inflammatory cytokines, such as IL-17, IL-22, and IL-23. Conclusion: Pharmacological modulation of cellular NAD⁺ levels could be a promising therapeutic approach for psoriasis-like skin disease.

Micro(nano)plastics (MNPs) are globally ubiquitous environmental pollutants that have become a growing concern for human health, but their potential role in human carcinogenesis remains to be determined. Over the past few years, MNPs have been identified as potential carcinogenic and mutagenic agents in various human samples as they induce oxidative stress, DNA damage, and immune dysregulation, which can alter the tumor microenvironment, thereby promoting cancer development and metastasis. Researchers are actively investigating the health risks posed by MNP particles in order to establish clearer links between MNP exposure and the onset of various human cancers. Although recent research suggests a potential tumorigenic connection between MNPs and some cancer types like skin, lung, breast and gastrointestinal cancers, further studies are required to clarify their long-term effects and specific mechanisms. In our review, we provide an overview of the current state of knowledge regarding the carcinogenic impacts of MNPs and the underlying molecular mechanisms through which MNP exposure may contribute to human cancer progression. Additionally, we highlight existing knowledge gaps and provide important recommendations for future research on the carcinogenic potential of MNPs.

Background Anemia is a common complication of chronic kidney disease. There are various causes of anemia in chronic kidney disease patients on hemodialysis. Secondary hyperparathyroidism is one of the less recognized causes of anemia in chronic kidney disease patients. Objectives The main objective of the study is to find the correlation between intact parathyroid hormone and hematocrit level in chronic kidney disease (CKD) patients undergoing hemodialysis. Method Verbal consent was taken from all the participants. Eighty participants between the age of 29 and 70 years with chronic kidney disease having indication of hemodialysis were included in this study. Hematocrit was measured by bioelectrical impedance method and serum intact parathyroid hormone was by using Chemi Luminescence Immuno Assay (CLIA) method. Result A weak reverse correlation was found between serum intact parathyroid level and hematocrit (r= -0.33). Conclusion In chronic kidney disease patient, there is reverse correlation between level of serum intact parathyroid and hematocrit level. This association may have clinical relevance in assessing the cause of unexplained low hemoglobin level in CKD patients.