Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora.

In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches' therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.

Hurdles to breakthrough in CAR T cell therapy of solid tumors.

Autologous T cells genetically engineered to express chimeric antigen receptor (CAR) have shown promising outcomes and emerged as a new curative option for hematological malignancy, especially malignant neoplasm of B cells. Notably, when T cells are transduced with CAR constructs, composed of the antigen recognition domain of monoclonal antibodies, they retain their cytotoxic properties in a major histocompatibility complex (MHC)-independent manner. Despite its beneficial effect, the current CAR T cell therapy approach faces myriad challenges in solid tumors, including immunosuppressive tumor microenvironment (TME), tumor antigen heterogeneity, stromal impediment, and tumor accessibility, as well as tribulations such as on-target/off-tumor toxicity and cytokine release syndrome (CRS). Herein, we highlight the complications that hamper the effectiveness of CAR T cells in solid tumors and the strategies that have been recommended to overcome these hurdles and improve infused T cell performance.

Curcumin-human serum albumin nanoparticles decorated with PDL1 binding peptide for targeting PDL1-expressing breast cancer cells.

In this research, programmed death ligand 1 (PDL1) binding peptide was used for targeted delivery of curcumin to high PDL1-expressing breast cancer cells. Human serum albumin-curcumin nanoparticles (HSA/Cur NP) were first prepared by desolvation method and then functionalized with PDL1 binding peptide. Peptide conjugation to HSA/Cur NPs was confirmed by Fourier transform infrared and UV-visible spectroscopy. The formation of HSA/Cur NP was characterized by transmission electron microscope and scanning electron microscope. The size and zeta potential were determined by dynamic light scattering. The average particle size of the HSA/Cur NPs and peptide-HSA/Cur NPs were 197 and 246.5 nm, respectively. Evaluation of cellular uptake showed enhanced internalization of peptide-HSA/Cur NPs in high PDL1-expressing cancer cells compared to HSA/Cur NPs. The cell viability and apoptosis determination demonstrated higher cytotoxicity of HSA/Cur NPs relative to free curcumin in breast cancer cells. Peptide conjugation to HSA/Cur NPs increased cytotoxicity significantly concerning high PDL1-expressing breast cancer cells. In conclusion, peptide-HSA/Cur NPs improved cellular uptake and cytotoxicity of HSA/Cur NPs in high PDL1-expressing breast cancer cells. These results suggest that PDL1 has potential to be used as a target for selective drug delivery and promising candidate for the treatment of PDL1-expressing breast cancer cells.