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The book starts with an introduction to and history of
myeloid-derived suppressor cells (MDSCs), followed by a description
of their differentiation, their role in the tumour microenvironment
and their therapeutic targeting. It closes with an outlook on
future developments. In cancer patients, myelopoiesis is perturbed
and instead of generating immunogenic myeloid cells (such as
dendritic cells, inflammatory macrophages and granulocytes), there
is an increase in highly immature MDSCs. These cells are
distributed systemically, resulting in general immunosuppression.
They also infiltrate tumours, promoting their progression and
metastasis by inhibiting the natural anti-tumour immune response.
As these cells also interact with classical anti-neoplastic
treatments, they have become major therapeutic targets in the
pharmaceutical industry and in oncology research.
The observation in the 1950s that nitrogen mustard and other toxic
chemicals could induce antitumor responses in patients with
refractory lymphoma initiated a massive search for active
chemotherapeutic agents. The initial observations stimulated a
search for new chemotherapeutic agents which might have increased
antitumor activity with less toxicity for normal tissues. To aid in
the search for these new chemicals and to attempt to distinguish
among the many toxic chemicals which might be candidates for
clinical studies, the National Cancer Institute, the pharmaceutical
industry, and the cancer research laboratories of most Western
nations developed systems for "screening" drugs for antitumor
activity. Perhaps the most extensive screening program was
established by the National Cancer Institute (1). This screening
program has evolved over the last two decades, an evolution which
has been repeatedly reviewed (2-5). Various screening programs in
use have examined over 500,000 compounds as potential anticancer
agents. From these, there are now approximately forty anticancer
drugs in clinical use. The utiliy of these compounds and their
toxicities have been reviewed on many occasions. It is now apparent
that more active and less toxic anticancer drugs are needed. It is
also clear that the current screening programs are identifying
compounds with similar levels of activity and with continuing
moderate to severe toxicity (6).
The observation in the 1950s that nitrogen mustard and other toxic
chemicals could induce antitumor responses in patients with
refractory lymphoma initiated a massive search for active
chemotherapeutic agents. The initial observations stimulated a
search for new chemotherapeutic agents which might have increased
antitumor activity with less toxicity for normal tissues. To aid in
the search for these new chemicals and to attempt to distinguish
among the many toxic chemicals which might be candidates for
clinical studies, the National Cancer Institute, the pharmaceutical
industry, and the cancer research laboratories of most Western
nations developed systems for "screening" drugs for antitumor
activity. Perhaps the most extensive screening program was
established by the National Cancer Institute (1). This screening
program has evolved over the last two decades, an evolution which
has been repeatedly reviewed (2-5). Various screening programs in
use have examined over 500,000 compounds as potential anticancer
agents. From these, there are now approximately forty anticancer
drugs in clinical use. The utiliy of these compounds and their
toxicities have been reviewed on many occasions. It is now apparent
that more active and less toxic anticancer drugs are needed. It is
also clear that the current screening programs are identifying
compounds with similar levels of activity and with continuing
moderate to severe toxicity (6).
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