Special Feature on Immunotherapy
Decades of Research Now Yielding
Results for Patients
An important milestone for cancer research was the discovery
that the immune system can identify and eliminate cancer cells
the way it does disease-causing pathogens.
The study of the structure and function of the immune system
is a field of research called immunology (see sidebar on
Key Players in the Immune System). Tumor immunology
(sometimes called cancer immunology) is the study of
interactions between the immune system and cancer cells.
The immune system naturally eliminates some cancers before
they become life threatening. Researchers, therefore, thought
that it should be possible to develop therapies that would
train a patient’s immune system to destroy their cancer. Such
therapies, referred to as immunotherapies, are now beginning
to revolutionize the treatment of some cancers, yielding both
remarkable and durable responses. Although getting to this
point has proven challenging, the field holds immense promise,
as discussed by cancer immunology pioneer Drew Pardoll.
Not all immunotherapies work in the same way. Some boost
the natural cancer-fighting ability of the immune system
by taking its brakes off, some increase the killing power of
the patient’s immune cells, and some flag cancer cells for
destruction by the immune system.
Researchers studying the intricacies of the immune system
are identifying novel immunotherapies and new ways to
utilize those that we already have, including the potential for
combining immunotherapies that operate in different ways
or combining immunotherapies with either radiation therapy
or other drugs. For example, it might be possible to design a
combination treatment that releases the brakes on the immune
system and simultaneously steps on the accelerator to enhance
immune cells’ killing power.
Releasing the Brakes on the Immune System
Immune cells called T cells (see sidebar on Key Players in the
Immune System) are naturally capable of destroying cancer
cells; however, many tumors develop sophisticated ways to
stop these T cells from functioning. One way this happens is
that T cells in the tumor microenvironment display on their
White blood cells, or leukocytes, are the cells of the immune
system that work together to protect the body from pathogens.
Some can also recognize cancer cells as dangerous to the body
and attack and destroy them. Here, we provide a very brief
description of the unique functions of some of the white blood
cells that have a central role in this process.
T cells, or T lymphocytes, are divided into two main types: those
that have the protein CD4 on their surface (CD4+ T cells) and
those that have the protein CD8 on their surface (CD8+ T cells).
CD4+ and CD8+ T cells both “identify” their target through a
groups of proteins on their surface called T-cell receptors.
CD8+ T cells are sometimes called cytotoxic T cells or killer T
cells. When they are called into action, they attack and destroy
CD4+ T cells respond differently to CD8+ T cells when called
into action. They do not kill their targets, rather they orchestrate
multiple other types of immune responses. For example,
they release factors, or cytokines, that direct the function of
other immune cells. CD4+ T cells that produce the cytokines
interleukin- 12 and interferon-γ, which help CD8+ T cells function,
are called T helper 1 cells, or Th1 cells.
A distinct subset of CD4+ T cells keeps other immune cells in
check, preventing them from attacking our own normal cells
and from over responding to pathogens. These cells are called
regulatory T cells, or Treg cells. Some cancers actively recruit
Treg cells to help shut down the anticancer immune response.
B cells, or B lymphocytes, respond to pathogens and cancer by
releasing factors called antibodies. Each B cell makes a single
antibody. Monoclonal antibodies, one of the most important
classes of anticancer therapy, are derived from the progeny
of a single B cell selected to produce one antibody with high
specificity for the therapeutic target of interest.
Dendritic cells have a central role as sentinels in the immune
system. They alert T cells to the presence of disease-causing
pathogens or cancer cells, triggering the T cells’ responses.
Natural killer cells, or NK cells, macrophages, and neutrophils
are additional specialized immune cell types that are some of
the “first responders” of the immune system. When called into
action, they release factors that kill their targets.