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Carcinogen exposure is strongly associated with enhanced cancer immunogenicity. Increased tumor mutational burden and resulting neoantigen generation have been proposed to link carcinogen exposure and cancer immunogenicity. However, the neoantigen-independent immunological impact of carcinogen exposure on cancer is unknown. Here, we demonstrate that chemical carcinogen-exposed cancer cells fail to establish an immunosuppressive tumor microenvironment (TME), resulting in their T cell-mediated rejection in vivo. A chemical carcinogen-treated breast cancer cell clone that lacked any additional coding region mutations (i.e., neoantigen) was rejected in mice in a T cell-dependent manner. Strikingly, the coinjection of carcinogen- and control-treated cancer cells prevented this rejection, suggesting that the loss of immunosuppressive TME was the dominant cause of rejection. Reduced M-CSF expression by carcinogen-treated cancer cells significantly suppressed tumor-associated macrophages (TAMs) and resulted in the loss of an immunosuppressive TME. Single-cell analysis of human lung cancers revealed a significant reduction in the immunosuppressive TAMs in former smokers compared with individuals who had never smoked. These findings demonstrate that carcinogen exposure impairs the development of an immunosuppressive TME and indicate a novel link between carcinogens and cancer immunogenicity., Introduction The advent of immune checkpoint blockade (ICB) therapy has greatly improved cancer treatment, especially for metastatic melanoma, non-small cell lung cancer and squamous cell carcinoma of the head and [...]

Learning how immune cells target tumours is crucial for cancer immunotherapy. The finding that a type of dendritic cell activates two sorts of T cell and coordinates their crosstalk sheds light on immune responses to tumours. Type 1 dendritic cells activate both CD4 and CD8 T cells., Author(s): Marianne Burbage, Sebastian Amigorena Author Affiliations: A dendritic cell multitasks to tackle cancer The generation of an efficient immune response against cancer is a multifaceted, multistep process. https://www.nature.com/articles/s41586-020-2611-3 , [...]

Bergman reaction and the energy splitting of the transformations of (Z)-hex-3-ene-1, 5-diyne (enediyence) into the singlet coupled biradical p-benzyne are reinvestigated at the CCSD(T) and CASPT2(g1) levels of theory for various basis sets using ab-initio. Underestimation of 5 Kcal/mol and 7 Kcal/mol is found for heat of formation on using small basis sets and CASPT2(g1) methods as compared to CCSD(T) level and method respectively. There are no significant differences in CCSD(T) and CASPT2(g1) methods for the energy splitting.

Anti-melanoma antibodies can be selected from fusion phage libraries, constructed from blood lymphocytes of melanoma patients immunized by autologous melanoma cells transduced by gamma-interferon gene. On testing by ELISA after panning the phage against live cultures of the autologous tumor cells, it showed melanoma-specific classes such as one that reacts almost only with the melanoma lines. A second tumor specific class does not react with the normal endothelial, melanocyte, and fibroblast cells but reacts with melanoma and other tumor lines. A third lineage-specific class reacts with melanocytes, melanoma lines, and the glioma line and not other lines.

Oncogene expression and cell proliferation were found to be regulatable when tetracycline-resistance operon regulatory system repressor's (tetR) binding to its cognate operator sequence takes place with tetracycline (Tet) or ATet derivative. Using tet to control simian virus 40 large tumor antigen (TAg) gene expression and transform pancreatic beta cells in transgenic mice, results showed the beta cells were dependent on TAg oncoprotein for proliferation.

The binding between a target sequence corresponding to element regulating viral lysis in human JC polyomavirus and cellular protein Pur-alpha decreases in the presence of another cellular protein YB-1, as revealed by band-shift assay studies. There is an enhancement in the binding of YB-1 with DNA by Pur-alpha and the viral early protein tumor antigen. The C-terminal of YB-1 and two specific fragments of the Pur-alpha protein are essential for affecting DNA binding by either of them.

The antigens Lea-Lex are produced enzymatically and are compared with Lea-Lea to characterize the epitope structure of the tumor-associated antigen, which is defined by mAb 43-9F. The evaluation is performed in a side-by-side immunoassay by the application of ST-421, mAbs43-9F and anti-Lea mAbCA3-F4. The hydrogen-nuclear magnetic resonance spectroscopy identifies the presence of enzymatically prepared Lea-Lex glycosphingolipids, which reveal the nature of the characterization.

DNA methylation, which modified methylated DNA sequence recognition and chromatin conformation of methylated segments, influenced DNA amplification. The effect of DNA methylation on gene amplification was observed in tumor cells in vivo. A rise in gene copy number per genome, which occurred in various cell systems, characterized gene amplification.

The ability of multimeric protein phosphatase 2A to neutralize nitrogen stimulated protein kinase ERK1 is compensated by the reaction of the protein phosphatase 2A with SV40 small tumor antigen (small t). The phosphatase also neutralizes the nitrogen stimulated protein kinase MEK1. MEK and ERK are stimulated by the transient expression of small t in CV-1 cells but do not influence the Raf activity. The increase in quiescent CV-1 cells occurs when there are small t and serum inductions

Lung tumors produced in transgenic mice, bearing the viral oncogene simian virus 40 (SV40) large tumor antigen, under transcriptional regulation of a promoter site from the human surfactant protein C (SP-C) gene, yielded murine lung epithelial (MLE) cells lines representing the distal bronchiolar and alveolar epithelium. Certain cell lines had microvilli cytoplasmic multivesicular bodies and multilamellar inclusion bodies.

The enhanced ostensible molecular mass of middle-sized tumor antigen (MTAg) on SDS/acrylamide gels, observed in the cell cycle regulation of pp60C-src in polyoma-transformed cells, was analyzed. The enhancement is because MTAg is temporarily phosphorylated during mitosis. The interaction of MTAg with cellular targets essential for cell transformation is controlled by the phosphorylation of P34cdc2 or an associated cell cycle-controlled kinase.

The L6 antigen is highly expressed on the surfaces of lung, breast, colon and ovarian carcinomas. Characterization studies on this antigen has been hampered due to its binding to other cell surface proteins. The gene coding for the L6 antigen was isolated and expressed in L6-negative cells. Analysis of the expressed antigen showed that it is 202 amino acids long, with four putative transmembrane domains and a glycosylated extracellular domain. Homology comparisons showed that the L6 antigen belongs to the family of integral membrane proteins which include CD63 and CO-029.