Assembly within the tumor center

Date:
August 4, 2020
Source:
Max-Planck-Gesellschaft
Summary:
Number of macrophages in tumor tissue enables prognosis of lung
tumor progression.



FULL STORY ==========================================================================
Both in the periphery and the center of lung tumors, characteristic accumulations of certain white blood cells, known as macrophages,
are often found. In this case they are called tumor-associated
macrophages. There are two populations with opposite effects on the tumor: while one is tumor-promoting, the second macrophage population inhibits
cancer growth. Scientists from the Max Planck Institute for Heart and
Lung Research and the Justus Liebig University in Giessen have now been
able to show that identifying the position and density of the two cell populations in the tumor tissue make it possible to predict the course
of the disease. This discovery may lead to new therapeutic possibilities.


========================================================================== Immune cells significantly influence the course of tumors. Depending
on the cell type, they can both promote and inhibit tumor growth. This
is particularly true for a group of macrophages, which accumulate in the
tumor center or the peripheral areas in sometimes large numbers. Depending
on their activation state, these so-called tumor-associated macrophages
can have a positive or negative influence on the course of the disease.

Scientists at the Max Planck Institute for Heart and Lung Research and the Justus Liebig University in Giessen discovered that the accumulation of a subpopulation of tumor-associated macrophages in a certain area can lead
to conclusions about the further course of the tumor disease. Rajkumar
Savai, project leader in the department "Development and Remodelling
of the Lung" and member of the Centre for Internal Medicine at
Justus Liebig University explains: "With lung tumors, it is usually
possible to distinguish the center of the tumor from the peripheral
area. Because a particularly large number of immune cells migrate
to the latter, we refer to this area as the invasive tumor margin."
For their study, the researchers used an elaborated microscopy technique
known as multiplex immunofluorescence microscopy. By this technique, macrophages could be safely identified. Furthermore their distance from neighbouring tumour cells was analysed. In addition, the Max Planck
researchers divided these cells into tumor-promoting and tumor-inhibiting tumor-associated macrophages based on certain properties. "We found that
more tumor-promoting cells were found in the invasive border area of
the tumor than tumor-inhibiting cells. Moreover, they were located more adjacent to the tumor cells," said Savai. "Based on tissue samples from
more than a hundred patients, we were then able to identify a pattern." According to this study, the survival rate in lung cancer patients was
lower, in particular when the tumor-promoting macrophages in the invasive marginal areas were particularly close to the tumor cells and at the same
time tumor- inhibiting macrophages were further away. The cell number
also had an influence on the prognosis of the patients: "If there were
fewer tumor-inhibiting macrophages in the tumor center, patients had a
lower probability for surviving. Overall, we found more tumor-promoting macrophages than tumor- inhibiting macrophages," Savai said.

The fact that tumor-promoting and tumor-inhibiting macrophages actually
have different activity patterns was shown when the Bad Nauheim scientists sequenced the cells' RNA. "We found that the two cell variants had very different gene expression profiles, even when compared with macrophages
from outside the tumor tissue," said Savai. The researchers identified
five candidates for biomarkers that could be used to predict survival
in lung cancer. "These biomarkers could prove to be very helpful for
the individual treatment strategy of lung cancer patients," emphasizes Friedrich Grimminger, head of the Giessen Lung Tumor Center and director
of the Medical Clinic IV/V at Justus Liebig University.

"Based on characteristic gene expression profiles of the tumor-associated macrophages, we have also identified factors in this study that
offer themselves as new target structures for specific therapeutic
approaches," adds Werner Seeger, Director of the Department "Development
and Reconstruction of the Lung" at the Max Planck Institute and the
Medical Clinic II of Justus Liebig University.


========================================================================== Story Source: Materials provided by Max-Planck-Gesellschaft. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Xiang Zheng, Andreas Weigert, Simone Reu, Stefan Guenther, Siavash
Mansouri, Birgit Bassaly, Stefan Gattenlo"hner, Friedrich
Grimminger, Soni Savai Pullamsetti, Werner Seeger, Hauke Winter,
Rajkumar Savai.

Spatial Density and Distribution of Tumor-Associated Macrophages
Predict Survival in Non-Small-Cell Lung Carcinoma. Cancer Research,
2020; canres.0069.2020 DOI: 10.1158/0008-5472.CAN-20-0069 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200804111446.htm

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