Tumor associated macrophages (TAMs) have been known as cells
which have protected and supported tumor cells. TAMs have been examined by many
researchers and there seems to be a slow but advancing opportunity to address
them and eliminate their influence[1].
From a recent paper by Etzerodt et al[2]:
Tumor-associated macrophages (TAMs) play critical roles
in tumor progression but are also capable of contributing to antitumor
immunity. Recent studies have revealed an unprecedented heterogeneity among
TAMs in both human cancer and experimental models. Nevertheless, we still
understand little about the contribution of different TAM subsets to tumor
progression. Here, we demonstrate that CD163-expressing TAMs
specifically maintain immune suppression in an experimental model of melanoma
that is resistant to anti–PD-1 checkpoint therapy. Specific depletion of the
CD163+ macrophages results in a massive infiltration of activated T cells and
tumor regression. Importantly, the infiltration of cytotoxic T cells was
accompanied by the mobilization of inflammatory monocytes that significantly
contributed to tumor regression. Thus, the specific targeting of CD163+ TAMs reeducates
the tumor immune microenvironment and promotes both myeloid and T cell–mediated
antitumor immunity, illustrating the importance of selective targeting of
tumor-associated myeloid cells in a therapeutic context.
This is a powerful observation and adds greatly to how these
protective macrophages can be handled. From Eureka[3]:
…new form of immunotherapy that has so far been tested on
mice makes it probable, that oncologists in the future may be able to
treat some of the patients who are not responding to existing types of
immunotherapy. Instead of attacking the cancer cells directly, the new
technique target and remove a subtype of immune cells known as macrophages,
after which the immune system itself begins to attack the cancer. This is shown by a new study published in the Journal of
Experimental Medicine in which researchers from Aarhus University, Denmark,
have collaborated with colleagues in France, the UK and USA, to show that the
serious form of skin cancer 'malignant melanoma' can be defeated by using the
new method. This variant of skin cancer accounts for eighty per cent of all
deaths from melanomas. "We've studied what happens to the tumour when it is
exposed to targeted treatment that removes precisely ten per cent of the
macrophages that are supporting the cancer tumour instead of fighting it,"
says Anders Etzerodt, PhD and assistant professor in cancer immunology at the
Department of Biomedicine at Aarhus University…"The most important result
is that the depletion of this specific type of macrophage causes the tumour to
shrink, which is triggered by a subsequent mobilisation of new macrophages and,
ultimately, also an activation of the so-called T cells which attack the
tumour," says Anders Etzerodt. The type of macrophages which the researchers have
removed express a specific receptor, CD163, on the cell surface. Unlike other
macrophages, these are known to have an undesirable effect in connection with
cancer. Instead of recognising cancer cells as unwanted tissue, the macrophage
sees the tumours as normal tissue that needs help with regeneration. It is also
widely recognised that survival rates are worse if there are many macrophages,
which express the CD163 receptor in the tumour.
This capability may be significant in addressing a wide
variety of cancers.
[2] Etzerodt
et al, Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and
promotes T cell–mediated tumor regression, Jrl Experimental Medicine, August
2019
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