8.–12. 11. 2021
Časové pásmo: Europe/Prague

The relationship between PD-L1/PD-1/MHC-1/Her2/and other immune or oncogenic receptors

12. 11. 2021 9:49
Miniprezentace Biologické účinky a zdravotní hlediska Biologické účinky a zdravotní hlediska


Elham Parsimehr (Biofyzikální ústav AV ČR, v.v.i.)


Cancer cells create distinct pathways to escape immune monitoring and are steadily expanding. Cytotoxic innate and adaptive immune cells can regulate the development of carcinoma by quite different receptors. At present, several costimulating molecules have discoverd , such as t-cell Immunoglobulin, the programmed death 1 (PD-1)/programmed ligand 1 (PD-L1) axis and lymphocytic-activating gene-3 (LAG3), HER2 (human epidermal growth factor receptor 2) which act alone or in concert to keep T cells in check and enable tumor cells to escape, with the different effect depending on the kind and stage of cancer.
These molecules' interactions can be correlated or anti-correlated, resulting in immunosuppressive and immunostimulatory responses. PD-L1 expression is now regarded as one of the most significant indicators for predicting ICI impact. As evidence of these findings, Cytoplasmic DNA potently activates the cGAS/STING pathway and PD-L1 expression (currently considered as a „negative“ response), while DNA damage also leads to enhanced HLA-neoantigen presentation (positive response). In a very simplified scenario, the PD-L1 receptor on the tumor (and some immune) cell surface interacts with its PD-1 ligand on T lymphocytes (or other immune cells), inhibit their proliferation, and suppresses the anti-tumor immune response. KPNB1 is a nuclear receptor responsible for the nuclear transport of HER2. Interestingly, anticorrelation between PD-L1 and Her2 points to a possible competition of these important oncoproteins for KPNB1 transporter.
According to most studies, high expression of Oncogene (HER2) is frequently related to deficient expression of antigen processing machine components of MHC Class I via RAS/MAPK signaling in different cancer types.
T cells co-expressing LAG3 and PD-1 are significantly exhausted compared with T cells that express LAG3 or PD-1 alone.Also, LAG-3 and PD-L1 synergized to regulate T-cell activity, producing immunological resistance. Targeted drugs (like IMP321) that inhibit LAG3/MHCII interaction increase tumor-related CD8 production and cytokines. Thus, many cancer therapies can target the balance of these responses.
The determination of oncogenic status (Epidermal growth factor receptor (EGFR), programmed death-ligand 1 (PD-L1), HER2, etc.) is required for combination treatments that of cancers.

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Hlavní autoři

Elham Parsimehr (Biofyzikální ústav AV ČR, v.v.i.) Lucie Dobešová (Biofyzikální ústav AV ČR, v.v.i.) Jiří Toufar (Biofyzikální ústav AV ČR, v.v.i.) Eva Pagáčová (Biofyzikální ústav AV ČR, v.v.i.) Olga Kopečná (Biofyzikální ústav AV ČR, v.v.i.) Iva Falková (Biofyzikální ústav AV ČR, v.v.i.) Alena Bačíková (Biofyzikální ústav AV ČR, v.v.i.) Michael Hausmann (Kirchhoff-Institute for Physics, University of Heidelberg) Martin Falk (Biofyzikální ústav AV ČR, v.v.i.)

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