Tumors may modulate host immunity partly through hypoxia-induced sympathetic bias

Medical Hypotheses
A Joon YunPatrick Y Lee

Abstract

Hypoxia can occur in solid tumors when oxygen demand from rapid tumor growth outstrips the blood supply. Once thought to be merely a consequence of tumor physiology, more recent evidence suggests that hypoxia may also be a tumor adaptation to promote its own survival. For example, hypoxic conditions generate local transcriptional changes that enhance angiogenesis and glycolysis, processes that directly promote tumor growth. We hypothesize that maladaptive local chemoreceptor host response to hypoxia may contribute to a shift in immune balance that favors cancer survival. Specifically, we propose that hypoxia in the tumor microenvironment activates local adrenergic activity which in turn inhibits Th1 function while favoring Th2 function. Th1 function is vital to the host defense against cancer, and Th1 depletion is associated with increased cancer risk. In our view, the sympathetic bias induces Th2 bias independent of the direct immunomodulatory effects of tumor-derived cytokines. The hypoxia-induced local adrenergic response may be part of a broad tumor adaptation that enables its evasion of host immune surveillance. That the host response of Th2 bias is so reflexively linked to hypoxia may reflect the likelihood that trauma, r...Continue Reading

References

Jan 1, 1992·Biomaterials, Artificial Cells, and Immobilization Biotechnology : Official Journal of the International Society for Artificial Cells and Immobilization Biotechnology·S A HoldenT S Herman
Jul 1, 1991·The International Journal of Neuroscience·E WeiheJ Krekel
Jul 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·G L SemenzaS E Antonarakis
Dec 1, 1988·Brain, Behavior, and Immunity·D L Felten, S Y Felten
Oct 1, 1995·The Journal of Clinical Investigation·V K SomersF M Abboud
Jan 20, 1995·The Journal of Biological Chemistry·G L Wang, G L Semenza
Jun 1, 1994·Cancer Metastasis Reviews·B A Teicher
Jan 1, 1993·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·M HöckelP Vaupel
Nov 1, 1996·European Journal of Immunology·S SubervilleL Baud
Sep 18, 1997·The Journal of Clinical Investigation·P Panina-BordignonF Sinigaglia
Dec 1, 1996·General Pharmacology·O FardelA Guillouzo
Oct 22, 1998·Metabolism: Clinical and Experimental·D J TorpyD A Papanicolaou
Dec 5, 1998·International Journal of Immunopharmacology·D W MullinsK D Elgert
Apr 8, 1999·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·D T Graves
Mar 21, 2002·Nature Reviews. Cancer·Adrian L Harris
Mar 29, 2002·Medical Oncology·P VaupelM Hoeckel
Jul 13, 2002·Annals of the New York Academy of Sciences·Ilia J Elenkov, George P Chrousos
Oct 25, 2002·International Journal of Cancer. Journal International Du Cancer·Barbara BachtiaryRichard Pötter
May 13, 2003·Obesity Research·Katherine EspositoDario Giugliano
Aug 30, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mary VarterasianDiane Healey
Feb 24, 1956·Science·O WARBURG
Apr 22, 2015·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Ali Kabir

❮ Previous
Next ❯

Citations

Apr 14, 2006·Chemotherapy·Jacek R Wilczyński
Sep 8, 2010·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Bina Raju, Salah O Ibrahim
Dec 3, 2016·Frontiers in Molecular Neuroscience·Eric C WoolfAdrienne C Scheck

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Cancer Metabolic Reprogramming (Keystone)

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Cancer Metabolic Reprogramming

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.