한빛사논문
- 조회296
Ellis L. Reinherz a,b,c,1, Wonmuk Hwang d,e,f,1, and Matthew J. Lang g,h,1
aLaboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115
bDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115
cDepartment of Medicine, Harvard Medical School, Boston, MA 02115
dDepartment of Biomedical Engineering, Texas A&M University, College Station, TX 77843
eDepartment of Materials Science and Engineering, Texas A&M University, College Station, TX 77843
fDepartment of Physics and Astronomy, Texas A&M University, College Station, TX 77843
gDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235
hDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37235
1Corresponding author: correspondence to Ellis L. Reinherz, Wonmuk Hwang or Matthew J. Lang
Abstract
T cell receptors (TCR) on cytolytic T lymphocytes (CTLs) recognize "foreign" antigens bound in the groove of major histocompatibility complex (MHC) molecules (H-2 in mouse and HLA in human) displayed on altered cells. These antigens are peptide fragments of proteins derived either from infectious pathogens or cellular transformations during cancer evolution. The conjoint ligand formed by the foreign peptide and MHC, termed pMHC, marks an aberrant cell as a target for CTL-mediated destruction. Recent data have provided compelling evidence that adaptive protection is achieved in a facile manner during immune surveillance when mechanical load consequent to cellular motion is applied to the bond formed between an αβ TCR and its pMHC ligand arrayed on a disease-altered cell. Mechanobiology maximizes both TCR specificity and sensitivity in comparison to receptor ligation in the absence of force. While the field of immunotherapy has made advances to impact the survival of cancer patients, the latest information relevant to T cell targeting and mechanotransduction has yet to be applied for T cell monitoring and treatment of patients in the clinic. Here we review these data, and challenge scientists and physicians to apply critical biophysical parameters of TCR mechanobiology to the medical oncology field, broadening treatment success within and among various cancer types. We assert that TCRs with digital ligand-sensing performance capability directed at sparsely as well as luminously displayed tumor-specific neoantigens and certain tumor-associated antigens can improve effective cancer vaccine development and immunotherapy paradigms.
논문정보
- Perspective
- 2023년 07월 (BRIC 등록일 2023-06-23)
- 국외 연구진
- 생명과학 > 구조생물 및 생물물리학
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