Human Physiology, 14th edition (2016)

520 Chapter 15

the early 1970s to describe the proposed role of the immune

system in fighting cancer. According to this concept, tumor

cells frequently appear in the body but are normally recog-

nized and destroyed by the immune system before they can

cause cancer.

However, tumors can evade immune surveillance by sup-

pressing immunity. Tumor cells produce and secrete immuno-

suppressive molecules, including transforming growth factor

beta (TGF b ) and FAS ligand (which binds to FAS and stim-

ulates apoptosis of lymphocytes, as previously described).

Also, the environment of the tumor can have a high popula-

tion of regulatory T lymphocytes, which secrete TGF b and

interleukin-10 to suppress the immune responses to the tumor

cells.

Natural Killer Cells

Hairless mice of a particular strain genetically lack a thymus

and T lymphocytes, yet these mice do not appear to have an

especially high incidence of tumor production. This surpris-

ing observation led to the discovery of natural killer (NK)

cells, which are lymphocytes that are related to, but distinct

from, T lymphocytes. The NK cells are lymphocytes that are

considered to be part of the innate immune system. Unlike the

B and T lymphocytes that are part of the adaptive immune sys-

tem, NK cells do not have the great receptor diversity gener-

ated by gene rearrangements to provide receptors for particular

antigens. Instead, the NK cells display an array of receptors

inherited through the germ cells (sperm and egg) that can tar-

get malignantly transformed cells and cells infected with intra-

cellular pathogens, such as viruses. Also, the NK cells have

inhibitory receptors that interact with MHC class 1 molecules

on the person’s own cells to provide tolerance to “self” and

prevent autoimmune attack.

Resting NK cells release cytokines, including interferon-

g and others; they also contain intracellular granules with

granzymes and perforin. Thus, like killer T lymphocytes

(section 15.3), they can destroy target cells by cell-to-cell

contact; unlike killer T lymphocytes, NK cells can do this

efficiently without prior exposure to the foreign antigens.

However, in order for NK cells to be fully effective, they must

first be activated by interferon- a , interferon- b , and other pro-

inflammatory cytokines.

NK cells can be activated by cytokines released by den-

dritic cells and by the cells of the adaptive immune system.

Once activated, the NK cells release interferon- g and other

cytokines that help activate macrophages and the cells of the

adaptive immune system. Because NK cells do not require

prior exposure to foreign antigens, they can provide a first

line of innate, cell-mediated defense that is subsequently

backed up by the adaptive, specific immune responses of

killer T lymphocytes. Cytokines released by both NK cells

and the cells of the adaptive immune system also enlist

phagocytic neutrophils and macrophages to the site of

immune attack.

Figure 15.22 T cell destruction of a cancer cell. In
this colorized scanning electron micrograph, the killer T cell
(orange) induces the apoptosis (programmed cell death) of a
cancer cell, colored mauve. The apoptosis of the cancer cell is
shown by its budding of vesicles, or apoptotic bodies.

Killer T cell

Cancer cell

CLINICAL APPLICATION

Humanized monoclonal antibodies for cancer treatments

are antibodies against particular tumor antigens that are

bioengineered chimeric (composed of genetically different

parts) mouse/human hybrids. These chimeric antibodies

are grown in mice, but the portion that binds to the anti-

gen is grafted onto a human antibody. Examples include

rituximab (for the treatment of non-Hodgkin’s lymphoma,

chronic lymphocytic leukemia, and others); trastuzumab

(for the treatment of HER2/neu receptor-positive breast

cancers); and bevacizumab (for the treatment of colorec-

tal, lung, and other cancers). Bioengineering has also made

available interleukin -2 ( IL-2 ) and interferons for medical

uses.

Adoptive cell transfer therapies for cancer involve

harvesting a patient’s T cells and using them to combat

the patient’s cancer. For example, a melanoma generates

T cells that are specific for the cancer’s antigens. These

can be harvested from the tissues surrounding the mela-

noma, stimulated to proliferate in vitro by IL-2, and then

put back into the tumor area. To prevent these anti-tumor

T cells from being suppressed by T reg cells, the patient’s

immune system has previously been repressed by radiation

or chemotherapy. This tumor-infiltrating lymphocyte ( TIL )

therapy has proven successful for the treatment for mela-

noma, but so far not for the treatment of other cancers. A

related approach, called chimeric antigen receptor ( CAR )

therapy, involves the patient’s own T cells that have been

given artificially created T cell receptors modified to target

tumor antigens.