INSIGHTS | P E R S P E C T I V E S
ASTRONOMY
How young stars grow and become focused Observations 18 years apart capture early changes of a massive star must then be found. Hydrodynamic collimation by the rotationMagnetically driven and collimated jet assive stars are the enigally flattened circumstellar matter matic big beasts of the has been invoked for this (see the Infalling stellar jungle. Although figure). Simulations and observaMagnetic material rare, they make up for tions have shown that radiation accretion fow this through their propressure acting on an accretion digious output of hard disk actually generates a wind in radiation and kinetic energy the disk plane rather than perpenfrom winds, and their explosive dicular to it (6). Accretion disk demise as supernovae. The latCarrasco-González et al. claim Swollen, cool protostar ter disperse heavy elements such to have seen a transition from as iron throughout interstellar an initially isotropic outflow to a space ready for incorporation in more collimated jet via changes the next generations of stars and in the morphology seen in radio planets, and of course, ourselves. continuum images taken 18 years When present in large numbers apart. The change in the shape of in a galaxy, their combined efthe radio free-free emission from Hydrodynamic fect can disrupt the interstelionized gas is backed up by simiRadiatively Infalling collimation driven wind material lar material to such an extent as lar changes in the distribution of to change the very nature of the spots of water maser emission. galaxy itself. These energetic outThey model the changes by asflows are present even during the suming an initially isotropic wind birth of massive stars. Indeed, this that would most naturally be exAccretion disk is one of the main reasons why plained by a radiatively driven Hot protostar understanding their formation wind from the central star. This from the gravitational collapse is then collimated hydrodynamiof interstellar clouds is so chalcally by a toroidal surrounding lenging. However, new sensitive, medium. Massive stars are known high-resolution facilities are being to have such radiatively driven brought to bear on the problem. winds once on the main seOn page 114 of this issue Carrascoquence, but these have speeds of González et al. (1) present radio Getting focused. Illustration of the two types of mechanisms that may give rise thousands of kilometers per secobservations using the upgraded to collimated outflows from massive protostars: magnetic and radiative. ond, and their density is too low Jansky Very Large Array (JVLA). to explain the outflows seen durRapid changes in the distribution of the some of the radiation pressure like a safety ing the formation stage. Where jet speeds ionized gas flowing out at high speed from valve (3, 4). What drives and collimates these have been directly measured for massive a massive young star could provide new outflows is one of the big unsolved problems protostars, they are found to be several insights into the birth pangs of these astroin star formation, particularly for high-mass hundreds of kilometers per second (7), simiphysical objects. protostars. Two classes of mechanisms preslar to those seen in the low-mass, magnetiOvercoming the strong outward radiaent themselves: magnetic and radiative. cally driven jets. These speeds are similar to tion pressure of these stars, which can be up Magneto-hydrodynamic mechanisms, often those required in Carrasco-González et al.’s to a million times more luminous than our invoking a magnetic field generated by the model. A jet arising from a different masSun, is key to building up the stellar mass. star itself, have long been thought to be resive protostar has also been seen to exhibit In recent years, the role of accretion via a sponsible for the highly collimated magnesynchrotron emission, which also implies a rotating disk has come to the fore as a way tized jets seen in low-mass protostars (5). magnetic origin (8). to transport large amounts of material past This mechanism is potentially problematic So there appear to be some contradictions the intense radiation field onto the growing for massive stars because once they are here, with the outflow properties being more star (2). As with most astrophysical accresettled into their hydrogen-burning mainconsistent with moderately fast, highly coltion disks, jets and/or bipolar outflows are sequence phase, they do not have strong limated, magnetically driven jets, whereas expected to be driven outwards along the magnetic fields. Their high surface temperathe star is expected to be nonmagnetic and rotation axis. These can then punch holes in tures prevent convection currents occurring dominated by radiation pressure. However, the surrounding in-falling cloud, releasing in their envelopes that can generate strong theoretical studies have shown that if promagnetic fields via a dynamo effect in stars tostars with masses in the range of 5 to 20 like the Sun. Radiation pressure could drive solar masses accrete at high rates, then the School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, UK. E-mail: [email protected] the outflows, but a collimating mechanism protostar swells up and is much cooler (9). By M. G. Hoare
44
sciencemag.org SCIENCE
3 APRIL 2015 • VOL 348 ISSUE 6230
Published by AAAS
ILLUSTRATION: P. HUEY/SCIENCE
Downloaded from www.sciencemag.org on April 2, 2015
M
Such an object would be convective and generate strong magnetic fields that could then drive and collimate protostellar jets. This also naturally explains why these luminous, but cool, protostellar objects do not ionize the wider surroundings. Such a scenario has been shown to match the observed distribution and lifetimes of massive protostars seen in the Milky Way (10). The object discussed by CarrascoGonzález et al. is currently only about 300 times the total luminosity of the Sun (11), which corresponds to about 6 solar masses. This puts it currently in the mass range where it could be swollen, magnetic, and capable of driving a collimated jet. The observations of Carrasco-González et al. do not actually rule out the possibility that the flow was always collimated, because the first epoch observations show an unresolved point source. If so, then we may just be seeing a new blob emerge down the jet similar to the behavior that is common in other types of astrophysical jets, such as those arising from black hole sources. The remaining questions will soon be addressed by other new high-resolution facilities. Higher-resolution radio studies of the ionized gas will come from the e-MERLIN array in the United Kingdom, while the Atacama Large Millimeter Array (ALMA) array in Chile will provide the corresponding view of the surrounding molecular material to determine if a confining torus is present, as well as the accretion disk. ALMA will also probe the kinematics, but we will have to wait for the mid-frequency element of the Square Kilometre Array in South Africa to probe the motions of the ionized gas itself. The advance of numerical simulation should also enable self-consistent three-dimensional simulations of the disk-jet system that include the effects of both radiation and magnetic fields. Hence, the coming few years promise to unmask the inner workings of the formation of these objects that play such a central role in astrophysics. ■
IMMUNOLOGY
MULT1plying cancer immunity A soluble ligand of an innate immunoreceptor arms natural killers for tumor attack By Alexander Steinle1 and Adelheid Cerwenka2
I
mmunotherapy of cancer, based on natural killer (NK) cells, is an emerging field (1). Activation of these innate lymphocytes depends on signals emanating from receptors that recognize transformed cells. The extent and spectrum of receptor engagement by cognate ligands that tumors bear determines the outcome of NK cell responses, including direct cellular killing (through the release of cytolytic granules) and communication with other immune cells (through secreted cytokines). One potent activating NK cell receptor involved in the destruction of ligand-expressing transformed cells is natural-killer group 2, member D (NKG2D). Recently, however, an immunosuppressive role was attributed to persistently engaged NKG2D. On page 136 of this issue, Deng et al. (2) report that, contrary to expectations, release of a particular NKG2D ligand by tumor cells results in NK cell activation and enhanced tumor rejection in a mouse model. This remarkable result may open new treatment options for cancer patients.
ILLUSTRATION: V. ALTOUNIAN/SCIENCE
10.1126/science.aaa8915
NK cell
Tumor microenvironment
Tumor cell Macrophage
Immune response to cancer
REFERENCES
1. C. Carrasco-González et al., Science 348, 114 (2015). 2. M. R. Krumholz, R. I. Klein, C. F. McKee, S. S. Offner, A. J. Cunningham, Science 323, 754 (2009). 3. A. J. Cunningham, R. I. Klein, M. R. Krumholz, C. F. McKee, Astrophys. J. 740, 107 (2011). 4. R. Kuiper, H. W. Yorke, N. J. Turner, Astrophys. J. 800, 86 (2015). 5. A. Frank et al., in Protostars and Planets VI, H. Beuther, R. Klessen, C. Dullemond, Th. Henning, Eds. (Univ. of Arizona Press, Tucson, 2014), p. 451. 6. M. G. Hoare, Astrophys. J. 649, 856 (2006). 7. S. Curiel et al., Astrophys. J. 638, 878 (2006). 8. C. Carrasco-González et al., Science 330, 1209 (2010). 9. T. Hosokawa, K. Omukai, Astrophys. J. 691, 823 (2009). 10. B. Davies et al., Mon. Not. R. Astron. Soc. 416, 972 (2011). 11. P. Persi, M. Tapia, H. A. Smith, Astron. Astrophys. 445, 971 (2006).
NK cells of the innate immune system recognize danger by detecting stressed, transformed, or virus-infected cells through the receptor NKG2D. In 1999, NKG2D was described as expressed by almost all human cytotoxic lymphocytes, detecting cell stress– inducible molecules [called major histocompatibility complex (MHC) class I–related chain molecules (MICA/B)] on tumor cells. Upon binding to a ligand, NKG2D triggers an intracellular signaling pathway involving phosphatidylinositol 3-kinase (3, 4). Eight ligands for NKG2D have been identified in human, each bearing an MHC class I–like ectodomain that binds to NKG2D. The number of functional NKG2D ligands in mouse strains varies (5). Initial studies revealed NK cell–dependent rejection of tumor cells ectopically expressing retinoic acid early inducible-1 (RAE-1), a mouse NKG2D ligand (6, 7). These findings were extended using NKG2D-deficient mice that exhibited an impaired control of certain spontaneous tumors (8). The concept of NKG2D as an activating receptor was challenged recently by results showing that its chronic exposure to surface-attached NKG2D ligands leads to
Suppression of immune response
Overcoming immune suppression
Cell death
Cell death sMULT1
Ligand
RAE-1
Cytolytic proteins
NKG2D
Activation
Other factors Down-regulation
Cytolytic proteins Activation
Desensitization Affinity matters. Acute exposure of NKG2D receptors to ligands expressed by tumor cells leads to tumor cell death (left). Chronic exposure of RAE-1 on myeloid cells in the tumor microenvironment impairs NK cell antitumor activity (middle). sMULT1 binds with high affinity to NKG2D and blocks the desensitizing interaction with RAE-1. This restores tumoricidal activity of NK cells (right).
SCIENCE sciencemag.org
3 APRIL 2015 • VOL 348 ISSUE 6230
Published by AAAS
45
How young stars grow and become focused M. G. Hoare Science 348, 44 (2015); DOI: 10.1126/science.aaa8915
This copy is for your personal, non-commercial use only.
Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at www.sciencemag.org (this information is current as of April 2, 2015 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/348/6230/44.full.html This article cites 10 articles, 4 of which can be accessed free: http://www.sciencemag.org/content/348/6230/44.full.html#ref-list-1 This article appears in the following subject collections: Astronomy http://www.sciencemag.org/cgi/collection/astronomy
Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.
Downloaded from www.sciencemag.org on April 2, 2015
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ASTRONOMY
How young stars grow and become focused Observations 18 years apart capture early changes of a massive star must then be found. Hydrodynamic collimation by the rotationMagnetically driven and collimated jet assive stars are the enigally flattened circumstellar matter matic big beasts of the has been invoked for this (see the Infalling stellar jungle. Although figure). Simulations and observaMagnetic material rare, they make up for tions have shown that radiation accretion fow this through their propressure acting on an accretion digious output of hard disk actually generates a wind in radiation and kinetic energy the disk plane rather than perpenfrom winds, and their explosive dicular to it (6). Accretion disk demise as supernovae. The latCarrasco-González et al. claim Swollen, cool protostar ter disperse heavy elements such to have seen a transition from as iron throughout interstellar an initially isotropic outflow to a space ready for incorporation in more collimated jet via changes the next generations of stars and in the morphology seen in radio planets, and of course, ourselves. continuum images taken 18 years When present in large numbers apart. The change in the shape of in a galaxy, their combined efthe radio free-free emission from Hydrodynamic fect can disrupt the interstelionized gas is backed up by simiRadiatively Infalling collimation driven wind material lar material to such an extent as lar changes in the distribution of to change the very nature of the spots of water maser emission. galaxy itself. These energetic outThey model the changes by asflows are present even during the suming an initially isotropic wind birth of massive stars. Indeed, this that would most naturally be exAccretion disk is one of the main reasons why plained by a radiatively driven Hot protostar understanding their formation wind from the central star. This from the gravitational collapse is then collimated hydrodynamiof interstellar clouds is so chalcally by a toroidal surrounding lenging. However, new sensitive, medium. Massive stars are known high-resolution facilities are being to have such radiatively driven brought to bear on the problem. winds once on the main seOn page 114 of this issue Carrascoquence, but these have speeds of González et al. (1) present radio Getting focused. Illustration of the two types of mechanisms that may give rise thousands of kilometers per secobservations using the upgraded to collimated outflows from massive protostars: magnetic and radiative. ond, and their density is too low Jansky Very Large Array (JVLA). to explain the outflows seen durRapid changes in the distribution of the some of the radiation pressure like a safety ing the formation stage. Where jet speeds ionized gas flowing out at high speed from valve (3, 4). What drives and collimates these have been directly measured for massive a massive young star could provide new outflows is one of the big unsolved problems protostars, they are found to be several insights into the birth pangs of these astroin star formation, particularly for high-mass hundreds of kilometers per second (7), simiphysical objects. protostars. Two classes of mechanisms preslar to those seen in the low-mass, magnetiOvercoming the strong outward radiaent themselves: magnetic and radiative. cally driven jets. These speeds are similar to tion pressure of these stars, which can be up Magneto-hydrodynamic mechanisms, often those required in Carrasco-González et al.’s to a million times more luminous than our invoking a magnetic field generated by the model. A jet arising from a different masSun, is key to building up the stellar mass. star itself, have long been thought to be resive protostar has also been seen to exhibit In recent years, the role of accretion via a sponsible for the highly collimated magnesynchrotron emission, which also implies a rotating disk has come to the fore as a way tized jets seen in low-mass protostars (5). magnetic origin (8). to transport large amounts of material past This mechanism is potentially problematic So there appear to be some contradictions the intense radiation field onto the growing for massive stars because once they are here, with the outflow properties being more star (2). As with most astrophysical accresettled into their hydrogen-burning mainconsistent with moderately fast, highly coltion disks, jets and/or bipolar outflows are sequence phase, they do not have strong limated, magnetically driven jets, whereas expected to be driven outwards along the magnetic fields. Their high surface temperathe star is expected to be nonmagnetic and rotation axis. These can then punch holes in tures prevent convection currents occurring dominated by radiation pressure. However, the surrounding in-falling cloud, releasing in their envelopes that can generate strong theoretical studies have shown that if promagnetic fields via a dynamo effect in stars tostars with masses in the range of 5 to 20 like the Sun. Radiation pressure could drive solar masses accrete at high rates, then the School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, UK. E-mail: [email protected] the outflows, but a collimating mechanism protostar swells up and is much cooler (9). By M. G. Hoare
44
sciencemag.org SCIENCE
3 APRIL 2015 • VOL 348 ISSUE 6230
Published by AAAS
ILLUSTRATION: P. HUEY/SCIENCE
Downloaded from www.sciencemag.org on April 2, 2015
M
Such an object would be convective and generate strong magnetic fields that could then drive and collimate protostellar jets. This also naturally explains why these luminous, but cool, protostellar objects do not ionize the wider surroundings. Such a scenario has been shown to match the observed distribution and lifetimes of massive protostars seen in the Milky Way (10). The object discussed by CarrascoGonzález et al. is currently only about 300 times the total luminosity of the Sun (11), which corresponds to about 6 solar masses. This puts it currently in the mass range where it could be swollen, magnetic, and capable of driving a collimated jet. The observations of Carrasco-González et al. do not actually rule out the possibility that the flow was always collimated, because the first epoch observations show an unresolved point source. If so, then we may just be seeing a new blob emerge down the jet similar to the behavior that is common in other types of astrophysical jets, such as those arising from black hole sources. The remaining questions will soon be addressed by other new high-resolution facilities. Higher-resolution radio studies of the ionized gas will come from the e-MERLIN array in the United Kingdom, while the Atacama Large Millimeter Array (ALMA) array in Chile will provide the corresponding view of the surrounding molecular material to determine if a confining torus is present, as well as the accretion disk. ALMA will also probe the kinematics, but we will have to wait for the mid-frequency element of the Square Kilometre Array in South Africa to probe the motions of the ionized gas itself. The advance of numerical simulation should also enable self-consistent three-dimensional simulations of the disk-jet system that include the effects of both radiation and magnetic fields. Hence, the coming few years promise to unmask the inner workings of the formation of these objects that play such a central role in astrophysics. ■
IMMUNOLOGY
MULT1plying cancer immunity A soluble ligand of an innate immunoreceptor arms natural killers for tumor attack By Alexander Steinle1 and Adelheid Cerwenka2
I
mmunotherapy of cancer, based on natural killer (NK) cells, is an emerging field (1). Activation of these innate lymphocytes depends on signals emanating from receptors that recognize transformed cells. The extent and spectrum of receptor engagement by cognate ligands that tumors bear determines the outcome of NK cell responses, including direct cellular killing (through the release of cytolytic granules) and communication with other immune cells (through secreted cytokines). One potent activating NK cell receptor involved in the destruction of ligand-expressing transformed cells is natural-killer group 2, member D (NKG2D). Recently, however, an immunosuppressive role was attributed to persistently engaged NKG2D. On page 136 of this issue, Deng et al. (2) report that, contrary to expectations, release of a particular NKG2D ligand by tumor cells results in NK cell activation and enhanced tumor rejection in a mouse model. This remarkable result may open new treatment options for cancer patients.
ILLUSTRATION: V. ALTOUNIAN/SCIENCE
10.1126/science.aaa8915
NK cell
Tumor microenvironment
Tumor cell Macrophage
Immune response to cancer
REFERENCES
1. C. Carrasco-González et al., Science 348, 114 (2015). 2. M. R. Krumholz, R. I. Klein, C. F. McKee, S. S. Offner, A. J. Cunningham, Science 323, 754 (2009). 3. A. J. Cunningham, R. I. Klein, M. R. Krumholz, C. F. McKee, Astrophys. J. 740, 107 (2011). 4. R. Kuiper, H. W. Yorke, N. J. Turner, Astrophys. J. 800, 86 (2015). 5. A. Frank et al., in Protostars and Planets VI, H. Beuther, R. Klessen, C. Dullemond, Th. Henning, Eds. (Univ. of Arizona Press, Tucson, 2014), p. 451. 6. M. G. Hoare, Astrophys. J. 649, 856 (2006). 7. S. Curiel et al., Astrophys. J. 638, 878 (2006). 8. C. Carrasco-González et al., Science 330, 1209 (2010). 9. T. Hosokawa, K. Omukai, Astrophys. J. 691, 823 (2009). 10. B. Davies et al., Mon. Not. R. Astron. Soc. 416, 972 (2011). 11. P. Persi, M. Tapia, H. A. Smith, Astron. Astrophys. 445, 971 (2006).
NK cells of the innate immune system recognize danger by detecting stressed, transformed, or virus-infected cells through the receptor NKG2D. In 1999, NKG2D was described as expressed by almost all human cytotoxic lymphocytes, detecting cell stress– inducible molecules [called major histocompatibility complex (MHC) class I–related chain molecules (MICA/B)] on tumor cells. Upon binding to a ligand, NKG2D triggers an intracellular signaling pathway involving phosphatidylinositol 3-kinase (3, 4). Eight ligands for NKG2D have been identified in human, each bearing an MHC class I–like ectodomain that binds to NKG2D. The number of functional NKG2D ligands in mouse strains varies (5). Initial studies revealed NK cell–dependent rejection of tumor cells ectopically expressing retinoic acid early inducible-1 (RAE-1), a mouse NKG2D ligand (6, 7). These findings were extended using NKG2D-deficient mice that exhibited an impaired control of certain spontaneous tumors (8). The concept of NKG2D as an activating receptor was challenged recently by results showing that its chronic exposure to surface-attached NKG2D ligands leads to
Suppression of immune response
Overcoming immune suppression
Cell death
Cell death sMULT1
Ligand
RAE-1
Cytolytic proteins
NKG2D
Activation
Other factors Down-regulation
Cytolytic proteins Activation
Desensitization Affinity matters. Acute exposure of NKG2D receptors to ligands expressed by tumor cells leads to tumor cell death (left). Chronic exposure of RAE-1 on myeloid cells in the tumor microenvironment impairs NK cell antitumor activity (middle). sMULT1 binds with high affinity to NKG2D and blocks the desensitizing interaction with RAE-1. This restores tumoricidal activity of NK cells (right).
SCIENCE sciencemag.org
3 APRIL 2015 • VOL 348 ISSUE 6230
Published by AAAS
45
How young stars grow and become focused M. G. Hoare Science 348, 44 (2015); DOI: 10.1126/science.aaa8915
This copy is for your personal, non-commercial use only.
Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at www.sciencemag.org (this information is current as of April 2, 2015 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/348/6230/44.full.html This article cites 10 articles, 4 of which can be accessed free: http://www.sciencemag.org/content/348/6230/44.full.html#ref-list-1 This article appears in the following subject collections: Astronomy http://www.sciencemag.org/cgi/collection/astronomy
Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.
Downloaded from www.sciencemag.org on April 2, 2015
If you wish to distribute this article to others, you can order high-quality copies for your colleagues, clients, or customers by clicking here.
