title: Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell-Mediated Killing.
abstract: OBJECTIVE
  To provide the foundation for combining immunotherapy to induce tumor antigen-specific T cells with proton radiation therapy to exploit the activity of those T cells.
  
  
  METHODS
  Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences.
  
  
  RESULTS
  These studies show for the first time that (1) proton and photon radiation induced comparable up-regulation of surface molecules involved in immune recognition (histocompatibility leukocyte antigen, intercellular adhesion molecule 1, and the tumor-associated antigens carcinoembryonic antigen and mucin 1); (2) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells; and (3) cancer stem cells, which are resistant to the direct cytolytic activity of proton radiation, nonetheless up-regulated calreticulin after radiation in a manner similar to non-cancer stem cells.
  
  
  CONCLUSIONS
  These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Sofia R
authors.initials: SR
authors.lastname: Gameiro
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Malamas
authors.affiliation: Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bernstein
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kwong Y
authors.initials: KY
authors.lastname: Tsang
authors.affiliation: Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: April
authors.initials: A
authors.lastname: Vassantachart
authors.affiliation: Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Narayan
authors.initials: N
authors.lastname: Sahoo
authors.affiliation: Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Tailor
authors.affiliation: Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Pidikiti
authors.affiliation: Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York.
authors.forename: Chandan P
authors.initials: CP
authors.lastname: Guha
authors.affiliation: Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hahn
authors.affiliation: Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: jh241d@nih.gov.
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000532:radiotherapy; D037282:Calreticulin / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000528:radiation effects; D002817:Chordoma / Q000276:immunology / Q000532:radiotherapy; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000532:radiotherapy; D008297:Male; D018396:Mucin-1 / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000528:radiation effects; D017785:Photons / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000276:immunology / Q000532:radiotherapy; D061766:Proton Therapy / Q000379:methods*; D011879:Radiotherapy Dosage; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D037282:Calreticulin; D002272:Carcinoembryonic Antigen; D006680:HLA Antigens; D018396:Mucin-1; D018799:Intercellular Adhesion Molecule-1