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  • April 14, 2009
  • 07:29 AM

Tumor immunity: The Goldilocks approach

by iayork in Mystery Rays from Outer Space

We know that the immune system can destroy tumors. We also know, unfortunately, that by the time we see a tumor, immunity probably won’t destroy the tumor. There are lots of reasons for that. One is that tumors are essentially part of the normal body, so it’s normal for the immune system [...]... Read more »

Rizzuto, G., Merghoub, T., Hirschhorn-Cymerman, D., Liu, C., Lesokhin, A., Sahawneh, D., Zhong, H., Panageas, K., Perales, M., Altan-Bonnet, G.... (2009) Self-antigen-specific CD8 T cell precursor frequency determines the quality of the antitumor immune response. Journal of Experimental Medicine, 206(4), 849-866. DOI: 10.1084/jem.20081382  

  • April 9, 2009
  • 10:10 AM

Why are different tumors the same?

by iayork in Mystery Rays from Outer Space

Hierarchical clustering of breast carcinomas1

Something that’s puzzled me for years is why the same kinds of tumors tend to have the same kinds of immune evasion mechanisms. And I’m not going to give an answer, just trying to share the confusion a little.

What I mean is this:

It has been demonstrated that human tumors of distinct [...]... Read more »

  • April 6, 2009
  • 06:42 AM

Inflammation and cancer: Proof that the universe hates us?

by iayork in Mystery Rays from Outer Space

Metchnikov: “Lecons sur la pathologie” (1892)

There are times when you just feel like the universe is out to get you. For example, we know that inflammation can drive tumor formation; but a paper just came out that suggests reducing inflammation can also drive tumor formation. 1 It doesn’t seem fair.

I’ve previously mentioned the [...]... Read more »

Granville, C., Memmott, R., Balogh, A., Mariotti, J., Kawabata, S., Han, W., LoPiccolo, J., Foley, J., Liewehr, D., Steinberg, S.... (2009) A Central Role for Foxp3 Regulatory T Cells in K-Ras-Driven Lung Tumorigenesis. PLoS ONE, 4(3). DOI: 10.1371/journal.pone.0005061  

  • March 27, 2009
  • 09:26 AM

On diversity in rhinoviruses

by iayork in Mystery Rays from Outer Space

Human rhinoviruses (HRV) are tiny, highly variable viruses that are one of the main causes of the common cold.   Stephen Liggett’s group has analyzed all 99 human rhinovirus genomes in the ATCC and come up with all kinds of fascinating insights. 1

How diverse are HRV? What maintains diversity or  lack of [...]... Read more »

Palmenberg, A., Spiro, D., Kuzmickas, R., Wang, S., Djikeng, A., Rathe, J., Fraser-Liggett, C., & Liggett, S. (2009) Sequencing and Analyses of All Known Human Rhinovirus Genomes Reveals Structure and Evolution. Science. DOI: 10.1126/science.1165557  

  • March 26, 2009
  • 09:36 AM

HIV escape, one-on-one

by iayork in Mystery Rays from Outer Space

It’s well known that HIV mutates rapidly in infected patients in order to escape from the immune system. The mutations in HIV track with the peptides that bind to MHC class I in any particular patient. When the virus is transmitted to a new patient, though, those mutations don’t help it much, because [...]... Read more »

  • March 23, 2009
  • 08:59 AM

Controlling cancer by blocking exhaustion?

by iayork in Mystery Rays from Outer Space

Melanoma antigens

The other day I talked about about resurrecting the antiviral response in HIV patients. 1 Antiviral T cells in HIV (and other chronic immune responses) become exhausted: After long exposure to antigen, the cytotoxic T lymphocytes (CTL) become dysfunctional, incapable of mounting a potent response to the virus. This exhausted state is correlated [...]... Read more »

Yuan, J., Gnjatic, S., Li, H., Powel, S., Gallardo, H., Ritter, E., Ku, G., Jungbluth, A., Segal, N., Rasalan, T.... (2008) CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proceedings of the National Academy of Sciences, 105(51), 20410-20415. DOI: 10.1073/pnas.0810114105  

  • March 19, 2009
  • 09:39 AM

On systemic immunity in flies

by iayork in Mystery Rays from Outer Space

It was previously thought that Drosophila is unable to spread systemically an RNAi response, based on observations that endogenously expressed RNA hairpins do not spread from cell to cell. However, we demonstrate that, upon virus infection, infected cells spread systemically a silencing signal that elicits protective RNAi-dependent immunity throughout the organism. … In striking [...]... Read more »

Saleh, M., Tassetto, M., van Rij, R., Goic, B., Gausson, V., Berry, B., Jacquier, C., Antoniewski, C., & Andino, R. (2009) Antiviral immunity in Drosophila requires systemic RNA interference spread. Nature, 458(7236), 346-350. DOI: 10.1038/nature07712  

  • March 16, 2009
  • 07:04 AM

Controlling HIV by blocking exhaustion

by iayork in Mystery Rays from Outer Space

The immune system needs to be rigorously controlled, lest it break its banks and flood the body with destructive responses. Any immune stimulant carries its own brakes; a response to an antigen peaks and then crashes as fast as it accelerated. When the brakes fail, autoimmunity and immune-mediated damage can be more lethal [...]... Read more »

Velu, V., Titanji, K., Zhu, B., Husain, S., Pladevega, A., Lai, L., Vanderford, T., Chennareddi, L., Silvestri, G., Freeman, G.... (2008) Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature, 458(7235), 206-210. DOI: 10.1038/nature07662  

  • March 12, 2009
  • 07:27 AM

A successful trial of a malaria vaccine

by iayork in Mystery Rays from Outer Space

The point of a vaccine trial is to test whether the vaccine works.  If you get an answer to that question, the trial is a success.  The answer may be “No”, in which case the vaccine is a failure, but the trial would still be a success.  (The STEP HIV vaccine trial was therefore a [...]... Read more »

  • March 9, 2009
  • 08:49 AM

The next step in the HIV arms race?

by iayork in Mystery Rays from Outer Space

Any time a species meets some kind of barrier, there’s going to be selection to overcome that barrier.  In the case of pathogens, one major barrier they have to hurdle is their hosts’ immune systems.  What’s more, this isn’t a simple, static barrier.  Immune systems change on a day-to-day basis; and immune systems also change [...]... Read more »

  • March 5, 2009
  • 07:22 AM

On measles vaccination and capitalism

by iayork in Mystery Rays from Outer Space

Anti-vaccine loons often claim that the only reason for vaccinations is the capitalist system and the ill-gotten profits of vaccination.

Here’s data1 from that notorious hotbed of capitalism, the People’s Republic of China of 1965, when measles vaccination was introduced.  For Shanghai …

The incidence of morbidity associated with measles ranged from 909 to 3,510/100,000 persons during [...]... Read more »

  • March 2, 2009
  • 12:00 AM

Evolution snapshot: Frogs vs. virus

by iayork in Mystery Rays from Outer Space

A ranavirus epidemic in UK frogs may be driving evolution of the MHC class I region... Read more »

  • February 25, 2009
  • 11:27 AM

On undiscovered viruses

by iayork in Mystery Rays from Outer Space

How many viruses infect humans? Have we found them all? If not, how many more are there?

We conclude that it is extremely probable that new human viruses will continue to be discovered in the immediate future; we are not yet close to the end of the virus discovery curve.  …Current trends are consistent with a pool [...]... Read more »

Mark E.J. Woolhouse, Richard Howey, Eleanor Gaunt, Liam Reilly, Margo Chase-Topping, & Nick Savill. (2008) Temporal trends in the discovery of human viruses. Proceedings of the Royal Society B: Biological Sciences, 275(1647), 2111-2115. DOI: 10.1098/rspb.2008.0294  

  • February 24, 2009
  • 09:18 AM

More chemotherapy and tumor immunity

by iayork in Mystery Rays from Outer Space

U-118 Glioma cells 

In one of the earliest posts I made to Mystery Rays,  I commented on an exciting anti-tumor finding. 1  Basically, the suggestion was that when chemotherapy of tumors works, it doesn’t actually work by killing all the tumor cells; or at least not directly.  Instead, the authors said, chemo works because the dying tumor [...]... Read more »

James F. Curtin, Naiyou Liu, Marianela Candolfi, Weidong Xiong, Hikmat Assi, Kader Yagiz, Matthew R. Edwards, Kathrin S. Michelsen, Kurt M. Kroeger, Chunyan Liu.... (2009) HMGB1 Mediates Endogenous TLR2 Activation and Brain Tumor Regression. PLoS Medicine, 6(1). DOI: 10.1371/journal.pmed.1000010  

  • February 19, 2009
  • 09:46 AM

Google vs. influenza

by iayork in Mystery Rays from Outer Space

It seems that influenza is a popular target for internet-based research; perhaps because it’s so common and well-known that population trends can be picked up accurately this way.

Five Google.com scientists, and one from the CDC, have published evidence in Nature1 that Google search terms are accurate ways of measuring influenza epidemics.  Their influenza tool is [...]... Read more »

Jeremy Ginsberg, Matthew H. Mohebbi, Rajan S. Patel, Lynnette Brammer, Mark S. Smolinski, & Larry Brilliant. (2008) Detecting influenza epidemics using search engine query data. Nature, 457(7232), 1012-1014. DOI: 10.1038/nature07634  

  • February 16, 2009
  • 01:28 PM

Not merely bioweaponized, but mutualistic bioweaponized wasps

by iayork in Mystery Rays from Outer Space

A while ago I mentioned the truly spectacular symbiosis between some parasitic wasps and their weaponized internal viruses.   These wasps parasitize caterpillars and the like; and to subdue their prey, the wasps inject viruses into their prey, along with their own eggs. The viral immune evasion functions then block the caterpillar’s defenses, allowing the [...]... Read more »

A. Bezier, M. Annaheim, J. Herbiniere, C. Wetterwald, G. Gyapay, S. Bernard-Samain, P. Wincker, I. Roditi, M. Heller, M. Belghazi.... (2009) Polydnaviruses of Braconid Wasps Derive from an Ancestral Nudivirus. Science, 323(5916), 926-930. DOI: 10.1126/science.1166788  

  • February 12, 2009
  • 10:10 AM

On peer review and fraud

by iayork in Mystery Rays from Outer Space

Following the Wakefield fraud story, I’ve seen several blogs and blog commenters suggesting that The Lancet was at fault for failing to catch the fraud in the peer review process.  I (and I think most practicing scientists) don’t agree with that condemnation, which I think shows that many people outside the field don’t really understand [...]... Read more »

M. Rossner. (2008) A false sense of security. The Journal of Cell Biology, 183(4), 573-574. DOI: 10.1083/jcb.200810172  

  • February 10, 2009
  • 06:51 AM

Immune control of Hepatitis C virus and HIV: coincidence or plan?

by iayork in Mystery Rays from Outer Space

HCV protein associated with lipid droplets

Torsten Schaller, Research As Art)

Although there are quite a few viruses that infect and then persist in the infected animal for a long time, most of these viruses don’t cause a lot of problems during the persistent state. Herpesviruses, adenoviruses, and several other families can stick around for a [...]... Read more »

Eva Dazert, Christoph Neumann-Haefelin, Stéphane Bressanelli, Karen Fitzmaurice, Julia Kort, Jörg Timm, Susan McKiernan, Dermot Kelleher, Norbert Gruener, John E. Tavis.... (2009) Loss of viral fitness and cross-recognition by CD8 T cells limit HCV escape from a protective HLA-B27–restricted human immune response. Journal of Clinical Investigation. DOI: 10.1172/JCI36587  

  • February 3, 2009
  • 09:08 AM

Virus vs tumor (vs ninja vs pirate): Computational oncolysis

by iayork in Mystery Rays from Outer Space

“Jennerex” virus (green) replicating within

a tumor mass.

Viruses infect cells, and quite often (depending on the type of virus) destroy the cell they’re infecting. Usually having your cells destroyed is a bad thing for the host, because [...]... Read more »

  • January 29, 2009
  • 08:24 PM

Immune evasion as an antiviral target

by iayork in Mystery Rays from Outer Space

I know all my regular readers1 are expecting me to talk about the bombshell announcements that NK cells have memory, but I’ll put that off for a bit and instead quickly note a very cool advance on a story I’ve mentioned a few times before.

Interferons are among the most critical early warning and protective cytokines, [...]... Read more »

D. Basu, M. P. Walkiewicz, M. Frieman, R. S. Baric, D. T. Auble, & D. A. Engel. (2008) Novel Influenza Virus NS1 Antagonists Block Replication and Restore Innate Immune Function. Journal of Virology, 83(4), 1881-1891. DOI: 10.1128/JVI.01805-08  

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