Page 246 - Textbook of Pathology, 6th Edition

230 of these two subpopulation of lymphocytes and ii) Specific stimulation of the immune system was attemp-
macrophages. Activated macrophages mediate cytotoxicity ted next by immunising the host with irradiated tumour cells
by production of oxygen free radicals or by tumour necrosis but failed to yield desired results because if the patient’s
factor. tumour within the body failed to stimulate effective
ii) Humoral mechanism. As such there are no anti-tumour immunity, the implanted cells of the same tumour are
humoral antibodies which are effective against cancer cells unlikely to do so.
in vivo. However, in vitro humoral antibodies may kill iii) Current status of immunotherapy is focussed on
tumour cells by complement activation or by antibody- following three main approaches:
dependent cytotoxicity. Based on this, monoclonal antibody a) Cellular immunotherapy consists of infusion of tumour-
SECTION I
treatment is offered to cases of some non-Hodgkin’s specific cytotoxic T cells which will increase the population
lymphoma. of tumour-infiltrating lymphocytes (TIL). The patient’s
iii) Immune regulatory mechanism. In spite of host immune peripheral blood lymphocytes are cultured with interleukin-
responses, most cancers grow relentlessly. This is due to some 2 which generates lymphokine-activated killer cells having
of the following controlling mechanisms: potent anti-tumour effect.
a) During progression of the cancer, immunogenic cells may b) Cytokine therapy is used to build up specific and non-
disappear. specific host defenses. These include: interleukin-2,
b) Cytotoxic T-cells and NK-cells may play a self regulatory interferon-α and -γ, tumour necrosis factor-α, and
role. granulocyte-monocyte colony stimulating factor (GM-CSF).
c) Immunosuppression mediated by various acquired c) Monoclonal antibody therapy is currently being tried against
carcinogenic agents (viruses, chemicals, radiation). CD20 molecule of B cells in certain B cell leukaemias and
d) Immunosuppressive role of factors secreted by tumour lymphomas.
cells e.g. transforming growth factor-β.
The mechanisms of these immune responses are EFFECT OF TUMOUR ON HOST
schematically illustrated in Fig. 8.28. Malignant tumours produce more ill-effects than the benign

3. IMMUNOTHERAPY. Despite the existence of anti- tumours. The effects may be local, or generalised and more
tumour immune responses, the cancers still progress and widespread.
eventually cause death of the host. The immune responses 1. LOCAL EFFECTS. Both benign and malignant tumours
to be effective enough must eliminate the cancer cells more cause local effects on the host due to their size or location.
rapidly than their rate of proliferation and hence the role of Malignant tumours due to rapid and invasive growth
General Pathology and Basic Techniques
boosting the immune response or immunotherapy. potential have more serious effects. Some of the local effects
i) Non-specific stimulation of the host immune response of tumours are as under:
was initially attempted with BCG, Corynebacterium parvum i) Compression. Many benign tumours pose only a
and levamisole, but except slight effect in acute lymphoid cosmetic problem. Some benign tumours, however, due to
leukaemia, it failed to have any significant influence in any their critical location, have more serious consequences e.g.
other tumour. pituitary adenoma may lead to serious endocrinopathy; a
small benign tumour in ampulla of Vater may lead to biliary
obstruction.
ii) Mechanical obstruction. Benign and malignant tumours
in the gut may produce intestinal obstruction.
iii) Tissue destruction. Malignant tumours, both primary
and metastatic, infiltrate and destroy the vital structures.
iv) Infarction, ulceration, haemorrhage. Cancers have a
greater tendency to undergo infarction, surface ulceration
and haemorrhage than the benign tumours. Secondary
bacterial infection may supervene. Large tumours in mobile
organs (e.g. an ovarian tumour) may undergo torsion and
produce infarction and haemorrhage.
2. CANCER CACHEXIA. Patients with advanced and
disseminated cancers terminally have asthenia (emaciation),
and anorexia, together referred to as cancer cachexia
(meaning wasting). Exact mechanism of cachexia is not clear
but it does not occur due to increased nutritional demands
of the tumour. Possibly, cachectin or tumour necrosis factor
α (TNF-α) and interleukin-1 derived from macrophages play
Figure 8.28 Schematic illustration of immune responses in cancer. a contributory role in cachexia. Various other causes include
For details see the text (CTL = cytotoxic T-lymphocyte; NK cell = natural necrosis, ulceration, haemorrhage, infection, malabsorption,
killer cell; ADCC = antibody-dependent cellular cytotoxicity). anxiety, pain, insomnia, hypermetabolism and pyrexia.