Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer

BACKGROUND The immune contexture predicts prognosis in human colorectal cancer (CRC). Whereas tumour-infiltrating CD8+ T cells and myeloid CD16+ myeloperoxidase (MPO)+ cells are associated with favourable clinical outcome, interleukin (IL)-17-producing cells have been reported to correlate with severe prognosis. However, their phenotypes and functions continue to be debated. OBJECTIVE To investigate clinical relevance, phenotypes and functional features of CRC-infiltrating, IL-17-producing cells. METHODS IL-17 staining was performed by immunohistochemistry on a tissue microarray including 1148 CRCs. Phenotypes of IL-17-producing cells were evaluated by flow cytometry on cell suspensions obtained by enzymatic digestion of clinical specimens. Functions of CRC-isolated, IL-17-producing cells were assessed by in vitro and in vivo experiments. RESULTS IL-17+ infiltrates were not themselves predictive of an unfavourable clinical outcome, but correlated with infiltration by CD8+ T cells and CD16+ MPO+ neutrophils. Ex vivo analysis showed that tumour-infiltrating IL-17+ cells mostly consist of CD4+ T helper 17 (Th17) cells with multifaceted properties. Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release. Consistent with these findings, the presence of intraepithelial, but not of stromal Th17 cells, positively correlated with improved survival. CONCLUSIONS Our study shows the dual role played by tumour-infiltrating Th17 in CRC, thus advising caution when developing new IL-17/Th17 targeted treatments.

Planktonic foraminifera in the Maastrichtian of Hor-Hahar

The lengthy warm, stable climate of the Cretaceous terminated in the Campanian with a cooling trend, interrupted in the early and latest Maastrichtian by two events of global warming, at ~70-68 Ma and at 65.78-65.57 Ma. These climatic oscillations had a profound effect on pelagic ecosystems, especially on planktic foraminiferal populations. Here we compare biotic responses in the tropical-subtropical (Tethyan) open ocean and mesotrophic (Zin Valley, Israel) and oligotrophic (Tunisia) slopes, which correlate directly with global warming and cooling. The two warming events coincide with blooms of Guembelitria, an extreme opportunist genus best known as the main survivor of the Cretaceous-Paleogene (K-Pg) catastrophe. In the Maastrichtian, Guembelitria bloomed in the uppermost surface water above shelf and slope environments but failed to reach the open ocean as it did at K-Pg. The coldest interval of the late Maastrichtian (~68-65.78 Ma) is marked by an acme of the otherwise rare species Gansserina gansseri, a deep-dwelling keeled globotruncanid. The G. gansseri acme event can be traced from the deep ocean even onto the Tethyan slope, marking copious production and circulation of cold intermediate water. This acme is abruptly terminated by extinction of the species, a dramatic reversal attributed to a short-term global warming episode. This extinction corresponds precisely with the second bloom of Guembelitria that began ~300 kyr prior to the K-Pg event. The antithetical relationship between blooming of Guembelitria and the G. gansseri acme reflects planktic foraminiferal sensitivity to warm-cool-warm-cool climatic oscillations marking the end of the Cretaceous.

Quaternary planktonic foraminifera of DSDP Hole 72-517

Quaternary sediments were recovered at all four Sites at Leg 72. Planktonic foraminifers were abundant and well preserved, especially in the holes shielded from Antarctic Bottom Water (AABW) influence. The fauna belonged to the subtropical province marked by Globigerinoides ruber and to a lesser extent by Globorotalia inflata. Thirty planktonic foraminiferal species were distinguished, and a detailed study of the Site 517 stratigraphy was made. The Quaternary sequence of the Rio Grande Rise was subdivided slightly differently from the Bolli and Premoli Silva (1973) pattern. Five subzones were identified but some difficulties arose when a precise correlation became necessary in the subzones of the tropical provinces. Correlations could nevertheless be made, particularly with respect to the earliest Quaternary. Quaternary faunal data have been dated by isotopic stratigraphy (Vergnaud Grazzini et al.,1983) and partially contradict results previously published for this part of the Atlantic (Williams and Ledbetter, 1979). By studying the occurrence of planktonic foraminifers, we obtained more information about hydrologic variations during the Quaternary sequence of Hole 517; two broad periods were recognized. Finally, we identified the interaction between the Brazil Current and the subtropical convergence

Characterization of late Campanian and Maastrichtian planktonic foraminiferal depth habitats and vital activities based on stable isotopes

Depth habitats of 56 late Cretaceous planktonic foraminiferal species from cool and warm climate modes were determined based on stable isotope analyses of deep-sea samples from the equatorial Pacific DSDP Sites 577A and 463, and South Atlantic DSDP Site 525A. The following conclusions can be reached: Planoglobulina multicamerata (De Klasz) and Heterohelix rajagopalani (Govindan) occupied the deepest plankton habitats, followed by Abathomphalus mayaroensis (Bolli), Globotruncanella havanensis (Voorwijk), Gublerina cuvillieri Kikoine, and Laeviheterohelix glabrans (Cushman) also at subthermocline depth. Most keeled globotruncanids, and possibly Globigerinelliodes and Racemiguembelina species, lived at or within the thermocline layer. Heterohelix globulosa (Ehrenberg) and Rugoglobigerina, Pseudotextularia and Planoglobulina occupied the subsurface depth of the mixed layer, and Pseudoguembelina species inhabited the surface mixed layer. However, depth ranking of some species varied depending on warm or cool climate modes, and late Campanian or Maastrichtian age. For example, most keeled globotruncanids occupied similar shallow subsurface habitats as Rugoglobigerina during the warm late Campanian, but occupied the deeper thermocline layer during cool climatic intervals. Two distinct types of "vital effect" mechanisms reflecting photosymbiosis and respiration effects can be recognized by the exceptional delta13C signals of some species. (1) Photosymbiosis is implied by the repetitive pattern of relatively enriched delta13C values of Racemiguembelina (strongest), Planoglobulina, Rosita and Rugoglobigerina species, Pseudoguembelina excolata (weakest). (2) Enriched respiration 12C products are recognized in A. mayaroensis, Gublerina acuta De Klasz, and Heterohelix planata (Cushman). Isotopic trends between samples suggest that photosymbiotic activities varied between localities or during different climate modes, and may have ceased under certain environmental conditions. The appearance of most photosymbiotic species in the late Maastrichtian suggests oligotrophic conditions associated with increased water-mass stratification.

(Table 1) Comparison of adjacent Cenomanian black shales with green claystones from DSDP Hole 75-530A

Black shales possessing high concentrations of organic carbon (Foresman, 1978, doi:10.2973/dsdp.proc.40.111.1978) were deposited in many parts of the proto South Atlantic Ocean during the Cretaceous period (Bolli et al., 1978, doi:10.2973/dsdp.proc.40.104.1978). The way such sediments accumulated is not fully understood, but is likely to have occurred through a combination of low oxygen availability and abundant supply of organic matter. Thin, centimetre-thick layers of black shales are commonly interbedded with thicker layers of organic carbon-deficient, green claystones, as found in strata of Aptian to Coniacian age, at Deep Sea Drilling Project (DSDP) Site 530, in the southern Angola Basin (Hay et al., 1982, doi:10.1130/0016-7606(1982)93<1038:SAAOOC>2.0.CO;2) and elsewhere. These differences in carbon content and colour reflect the conditions of deposition, and possibly variations in the supply of organic matter (Summerhayes and Masran, 1983, doi:10.2973/dsdp.proc.76.116.1983; Dean and Gardner, 1982). We have compared, using organic geochemical methods the compositions of organic matter in three pairs of closely-bedded black and green Cenomanian claystones obtained from Site 530. Kerogen analyses and distributions of biological markers show that the organic matter of the black shales is more marine and better preserved than that of the green claystones.

Planktonic foraminifera of ODP Hole 107-654A

The late Miocene sediments of the Tyrrhenian ODP Site 654 encompass a deepening sequence which begins with glauconite shallow water sands followed by a rapid transition to deep water sediments and culminates with dolomitic mudstones associated with Messinian evaporites. The sequence compares well with the so-called 'Sahelian cycle' and with post-orogenic cycles recognized in peninsular Italy and Sicily. The studied interval, consisting of 55 m thick nannofossil oozes, belongs to the Globorotalia suterae subzone and lower part of the Globorotalia conomiozea Zone, indicating late Tortonian and early Messinian age, respectively. Biomagnetostratigraphic correlation assigns the Tortonian/ Messinian boundary an age of 6.44-6.45 Ma. In addition, six main events have been recognized, based on the range of keeled globorotaliids and coiling direction changes of keeled and unkeeled globorotaliids, which have been correlated to the geomagnetic time-scale. Comparison with North Atlantic sites and land sections of the Guadalquivir basin and northern Morocco provides good correlations with the events documented in these areas. In particular, Event IV, which predates the FO of Globorotalia conomiozea, may be used to recognize the Tortonian/Messinian boundary in extra-Mediterranean areas where G. conomiozea is missing. Variations in the distribution of different species of Globigerinoides are related to changes in the surficial marine environment. Although no clear trends can be recognized on the oxygen and carbon isotope records of Globigerinoides obliquus, the parallelism between the occurrence of low salinity species (G. sacculifer) and peaks of low 5180 values, as well as that of normal salinity species (G. obliquus) and peaks of high d18O values, suggests strong local changes of environmental conditions. The high amplitude of the fluctuations of d18O values suggests important variations in the salinity of the Tyrrhenian Sea, related to a rapidly changing water budget. The major feature of the carbon isotope record is a large decrease between 7.0 and 6.95 Ma, which therefore predates the 6.2 Ma global 'carbon shift'.

Cenozoic calcareous nannofossils from the Lesser Antilles Forearc Region

During Leg 110 of the Ocean Drilling Program, sediment was recovered from six sites in the vicinity of the Lesser Antilles Forearc. Hole 671B, drilled near the toe of the Barbados deformation front, was the first-ever penetration of the decollement between the underthrusting Atlantic Plate and the off scraped Barbados accretionary prism. Stratigraphic repetitions in sequence associated with tectonic movement along the decollement zone, first observed on DSDP Leg 78A, were further documented at four ODP Leg 110 sites. A significant biostratigraphic inversion is present at Site 671 at 128 mbsf in which upper Miocene sediments rest atop lower Pleistocene strata. Smaller repetitions in sequence are recorded at Sites 671, 673, 674, and 676. Leg 110 sediments range from middle Eocene to early Pleistocene in age. Pliocene/Pleistocene assemblages are generally well preserved; however, Miocene assemblages have undergone extensive dissolution at all Leg 110 sites. Paleogene sediments are sometimes recrystallized and the nannofossils contained within exhibit a range in preservation from poor to good.