Low-dose irradiation programs macrophage differentiation to an iNOS⁺/M1 phenotype that orchestrates effective T cell immunotherapy.

By Felix Klug, Hridayesh Prakash, P. Huber, T. Seibel, Noemi Bender, N. Halama, C. Pfirschke, Ralf-Holger Voss, C. Timke, L. Umansky and 8 more. Cancer Cell, 2013

1,032 citations recorded by the source corpus.

Inefficient T cell migration is a major limitation of cancer immunotherapy. Targeted activation of the tumor microenvironment may overcome this barrier. We demonstrate that neoadjuvant local low-dose gamma irradiation (LDI) causes normalization of aberrant vasculature and efficient recruitment of tumor-specific T cells in human pancreatic carcinomas and T-cell-mediated tumor rejection and prolonged survival in otherwise immune refractory spontaneous and xenotransplant mouse tumor models. LDI (local or pre-adoptive-transfer) programs the differentiation of iNOS⁺ M1 macrophages that orchestrate CTL recruitment into and killing within solid tumors through iNOS by inducing endothelial activation and the expression of TH1 chemokines and by suppressing the production of angiogenic, immunosuppressive, and tumor growth factors.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/b28adbb32a581c9eef40275d6d7e11979a0a08c3

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. A. Mantovani
2. P. Allavena
3. V. Schirrmacher
4. A. Sica
5. C. Garlanda
6. J. Pollard
7. F. Balkwill
8. D. Hanahan

In Oncology

1. P. Allavena
2. A. Mantovani
3. V. Schirrmacher
4. A. Sica
5. Lisa M. Coussens
6. M. Karin
7. J. Pollard
8. F. Balkwill

Citations in the corpus

• Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy (2016, neutral): “For example, some chemotherapeutics and other treatments shape clinical outcome by influencing tumor-host interactions to stimulate T cell immunosurveillance (Zitvogel et al., 2013; Klug et al., 2013; Shalapour et al., 2015).”
• The interaction of anticancer therapies with tumor-associated macrophages (2015, background): “In an interesting twist, neoadjuvant low-dose irradiation was found to normalize the tumor vasculature and to enhance recruitment of tumor-specific T cells in various cancer models (Klug et al., 2013).”
• From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review) (2018, positive): “inducible nitric oxide synthase+/M1) that then can orchestrate effective T-cell immunotherapy (42).”