Abstract

The objectives of this research are to determine: (1) why cells of the host immune system are often unable to mount an effective response against tumor cells even when those cells bear recognizable distinct tumor antigens; and (2) the effect of radiation on the host-tumor-cell interactions. This study focuses on the cellular interactions occurring between various types of host cells and between host and tumor cells in situ within the actual tumor, which we have confirmed to contain many tumor-reactive host immune cells. We are using multicellular tumor spherolds of EMT6/Ro mammary sarcoma cells, a relatively immunogenic BALB/c mouse tumor, and Line 1 cells, a weakly immunogenic BALB/c alveolar carcinoma, to study the ability of host immune cells to recognize tumor antigens, infiltrate tumors, and function within a tumor-like microenvironment. The technologies of centrifugal elutriation and immunofluorescent flow cytometry are being used to separate, identify, and purify the subpopulations of in situ host cells. We have determined that EMT6 tumor cells secrete a soluble factor which is highly suppressive to host immune cells and is probably a mechanism which allows this tumor to evade the immune system. (IP)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA028332-05
Application #
3168075
Study Section
Radiation Study Section (RAD)
Project Start
1980-06-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Connolly, Kelli A; Belt, Brian A; Figueroa, Nathania M et al. (2016) Increasing the efficacy of radiotherapy by modulating the CCR2/CCR5 chemokine axes. Oncotarget 7:86522-86535
Barlow, Margaret L; Cummings, Ryan J; Pentland, Alice P et al. (2016) Total-Body Irradiation Exacerbates Dissemination of Cutaneous Candida Albicans Infection. Radiat Res 186:436-446
Gerber, Scott A; Cummings, Ryan J; Judge, Jennifer L et al. (2015) Interleukin-12 preserves the cutaneous physical and immunological barrier after radiation exposure. Radiat Res 183:72-81
Lim, Joanne Yh; Brockstedt, Dirk G; Lord, Edith M et al. (2014) Radiation therapy combined with Listeria monocytogenes-based cancer vaccine synergize to enhance tumor control in the B16 melanoma model. Oncoimmunology 3:e29028
Gerber, Scott A; Lim, Joanne Y H; Connolly, Kelli A et al. (2014) Radio-responsive tumors exhibit greater intratumoral immune activity than nonresponsive tumors. Int J Cancer 134:2383-92
Majumder, Syamantak; Sowden, Mark P; Gerber, Scott A et al. (2014) G-protein-coupled receptor-2-interacting protein-1 is required for endothelial cell directional migration and tumor angiogenesis via cortactin-dependent lamellipodia formation. Arterioscler Thromb Vasc Biol 34:419-26
Lim, Joanne Y H; Gerber, Scott A; Murphy, Shawn P et al. (2014) Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8(+) T cells. Cancer Immunol Immunother 63:259-71
Martin, Daniel K; Uckermann, Ortrud; Bertram, Aiko et al. (2014) Differential growth inhibition of cerebral metastases by anti-angiogenic compounds. Anticancer Res 34:3293-302
Xu, Yuexin; Hyun, Young-Min; Lim, Kihong et al. (2014) Optogenetic control of chemokine receptor signal and T-cell migration. Proc Natl Acad Sci U S A 111:6371-6
Sedlacek, Abigail L; Gerber, Scott A; Randall, Troy D et al. (2013) Generation of a dual-functioning antitumor immune response in the peritoneal cavity. Am J Pathol 183:1318-1328

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