Perivascular tumor-associated macrophages and their role in cancer progression

Perivascular (Pv) tumor-associated macrophages (TAMs) are a highly specialized stromal subset within the tumor microenvironment (TME) that are defined by their spatial proximity, within one cell thickness, to blood vasculature. PvTAMs have been demonstrated to support a variety of pro-tumoral functions including angiogenesis, metastasis, and modulating the immune and stromal landscape. Furthermore, PvTAMs can also limit the response of anti-cancer and anti-angiogenic therapies and support tumor recurrence post-treatment. However, their role may not exclusively be pro-tumoral as PvTAMs can also have immune-stimulatory capabilities. PvTAMs are derived from a monocyte progenitor that develop and localize to the Pv niche as part of a multistep process which relies on a series of signals from tumor, endothelial and Pv mesenchymal cell populations. These cellular communications and signals create a highly specialized TAM subset that can also form CCR5-dependent multicellular ‘nest’ structures in the Pv niche. This review considers our current understanding of the role of PvTAMs, their markers for identification, development, and function in cancer. The role of PvTAMs in supporting disease progression and modulating the outcome from anti-cancer therapies highlight these cells as a therapeutic target. However, their resistance to pan-TAM targeting therapies, such as those targeting the colony stimulating factor-1 (CSF1)-CSF1 receptor axis, prompts the need for more targeted therapeutic approaches to be considered for this subset. This review highlights potential therapeutic strategies to target and modulate PvTAM development and function in the TME

Macrophages orchestrate the expansion of a proangiogenic perivascular niche during cancer progression

Tumor-associated macrophages (TAMs) are a highly plastic stromal cell type that support cancer progression. Using single-cell RNA sequencing of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT), we characterize a subset of these cells expressing lymphatic vessel endothelial hyaluronic acid receptor 1 (Lyve-1) that spatially reside proximal to blood vasculature. We demonstrate that Lyve-1+ TAMs support tumor growth and identify a pivotal role for these cells in maintaining a population of perivascular mesenchymal cells that express α-smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques, we show that mesenchymal cells maintain their prevalence in the growing tumor through proliferation and uncover a role for Lyve-1+ TAMs in orchestrating a selective platelet-derived growth factor–CC–dependent expansion of the perivascular mesenchymal population, creating a proangiogenic niche. This study highlights the inter-reliance of the immune and nonimmune stromal network that supports cancer progression and provides therapeutic opportunities for tackling the disease

Estuarine macrophytes and saltmarsh vegetation reflectance spectra collected at Wallis Lake (NSW, Australia)

Wallis Lake is a shallow estuarine lake system consisting of lakes and rivers with interconnecting channels. The lake is a significant environmental resource and is also used for recreational activities and aquaculture. In collaboration with participants from NSW DPI, CSIRO undertook a fieldwork campaign at Wallis Lake 12-16 May 2008 to fill in known gaps in saltmarsh, mangrove, seagrass and macro-algae spectra as well as abiotic backgrounds such as sand and mud. Benthic material were collected with an Eckman grab, where the structure and shape of the sample was retained. Samples were placed on a black neoprene mat and spectra were collected using a RAMSES spectroradiometer. The RAMSES spectroradiaometer system deployed at Wallis Lake consisted of two cosine collector sensors measuring downwelling irradiance (Ed) and one radiance collector measuring upwelling radiance (Lu). In situ spectral reflectance of intertidal and supratidal vegetation were collected with an ASD-FR FieldSpec Pro spectroradiometer system which measures over a range of 325 to 2500 nm. To fill in data gaps, additional supratidal substratum spectra were collected in September 2008 with an ASD FieldSpec Pro HandHeld spectroradiometer (www.asdi.com). Substratum irradiance reflectance was calculated as the ratio of the upwelling radiance (Lu) and the downwelling irradiance (Ed): Rsub = Lu/Ed Thus the substratum reflectance is a measure of the reflection of light from the target irrespective of the illumination quantity. All measurements were collected close to the target with a 5° fore-optic fitted to the optical fibre, limiting the instrument field of view (FOV) to that of the only the target. This was done to ensure that only pure end-member spectra were collected. Ed was defined by a spectralon panel at the same distance as the selected target. Above-water spectra were collected with the foreoptic mounted in a standard pistol-grip enabling accurate pointing of the fibre within its FOV boundaries. Reference spectra from the spectralon panel were collected at frequent intervals to compensate for the effects of variable atmospheric conditions on natural irradiance. Field spectral reflectance values were corrected for irradiance variations, assuming a linear change in irradiance over time, using these reference spectra. Data collected during this field campaign included: - Inherent optical properties (IOP) and apparent optical properties (AOP) measurements of water quality in representative waters of Wallis Lake and rivers _ Reflectance measurements of seagrasses, algae and mud/sand collected with a RAMSES - field spectrometer - GPS depth transect across Posidonia beds on the eastern boundary of Wallis Island. - A pseudo invariant feature (PIF) measurement on the Wallis Island airstrip was collected to assist in the atmospheric correction of the 2003 Quickbird imagery which had exhibited significant calibration issues and could not be successfully corrected for atmospheric effects by standard methodologies undertaken by CSIRO. The reflectance values collected at the airstrip was assumed to represent reflectance at the time when the satellite image was collected. - Terrestrial reflectance spectra of saltmarsh and mangrove species as well as other key species present were collected with an ASD field spectrometer for inclusion in the spectral library as well as for validation purposes

Intertidal and subtidal benthic reflectance spectra collected at Georgina Cay (Lihou Reef National Marine Park, Coral Sea Territory, Australia)

Field work was undertaken in the Lihou Reef National Marine Park (Coral Sea Territory, Australia, 17.583°S, 151.517°E) in December 2008. The aim of the remote sensing component of the field work was to collect in situ data for both remote sensing model parameterisation and for validation of remote sensing based results. Effort was placed on trying to characterise the (variations in) optical properties of the benthic substrates and vegetation that are part of the Lihou Reef Cay system (i.e. surrounding reefs and islands, respectively). Sample biotic and abiotic benthic types were sourced in situ in the intertidal- (exposed, above water) and the near-shore subtidal (submerged) zone. Benthic substratum reflectance spectra were measured from opportunistic samples collected in the intertidal and subtidal zone by snorkelers and divers. Spectral data was collected with an ASD FieldSpec Pro HandHeld spectroradiometer (http://www.asdi.com) which is designed for portability and measures over the range 325 to 1075 nm with a sampling interval of 1.4nm and a Full Width at Half Maximum (FWHM) resolution of 3nm. Substratum irradiance reflectance was calculated as the ratio of the upwelling radiance (Lu) and the downwelling irradiance (Ed): Rsub = Lu/Ed Thus the substratum reflectance is a measure of the reflection of light from the target irrespective of the illumination quantity. All measurements were collected close to the target with a 5° fore-optic fitted to the optical fibre, limiting the instrument field of view (FOV) to that of the only the target. This was done to ensure that only pure end-member spectra were collected. Ed was defined by a spectralon panel and at the same distance as the selected target. Above-water spectra were collected with the foreoptic mounted in a standard pistol-grip enabling accurate pointing of the fibre within its FOV boundaries. Reference spectra from the spectralon panel were collected at frequent intervals to compensate for the effects of variable atmospheric conditions on natural irradiance. Field spectral reflectance values were corrected for irradiance variations, assuming a linear change in irradiance over time, using these reference spectra. Additional data collected during this field campaign included: - Reflectance spectra of, intertidal and benthic substrates believed to be representative of the island/lagoon system using a non-submersible ASD FieldSpec handheld spectrometer as well as a submersible HydroRad spectrometer. - Measurements were made of the optical quality of the waters within the Lihou lagoon, the individual cay lagoons of Georgina, Anne, Lorna and Turtle cays as well as the surrounding open ocean locations