Veterinary Quarterly

ISSN: 0165-2176 (Print) 1875-5941 (Online) Journal homepage: http://www.tandfonline.com/loi/tveq20

Canine transmissible venereal tumour:

Cytogenetic origin, immunophenotype, and
immunobiology. A review
S. Mukaratirwa & E. Gruys
To cite this article: S. Mukaratirwa & E. Gruys (2003) Canine transmissible venereal tumour:
Cytogenetic origin, immunophenotype, and immunobiology. A review, Veterinary Quarterly,
25:3, 101-111, DOI: 10.1080/01652176.2003.9695151
To link to this article: http://dx.doi.org/10.1080/01652176.2003.9695151

Published online: 01 Nov 2011.

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101
Veterinary Quarterly 2003; 25(3): 101-111

Canine transmissible venereal tumour: cytogenetic origin,

immunophenotype, and immunobiology. A review
S. Mukaratirwa" and E. Gruys2
'University of Zimbabwe, Faculty of Veterinary Science, Department of Paraclinical Studies, P.O.
Box 167, Mount Pleasant, Harare, Zimbabwe

2Utrecht University, Faculty of Veterinary Medicine, Department of Pathology, P.O. Box 80158,
3508 TD Utrecht, The Netherlands

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TABLE OF CONTENTS

Summary and keywords

102

Introduction

102

Cytogenetic origin of canine transmissible venereal tumour (CTVT)

102

CTVT immunophenotype

103

CTVT immunobiology. A model for tumor immunology

104

CTVT associated-antigens and humoral immunity

Cell mediated immunity and major histocompatibility (MHC) antigens

104
105

Evaluation of CTVT stage

107

CTVT immunotherapy

107

Conclusion

108

References

108

3Corresponding author

Address: Department of Paraclinical Veterinary Studies, Faculty of Veterinary Science, University

of Zimbabwe, P.O. Box MP 167, Mount Pleasant, Harare, Zimbabwe

E-mail: tmukaratirwa@vet.uz.ac.zw
Fax:
+263 4 333683

102

Canine transmissible venereal tumour: cytogenetic origin,

immunophenotype, and immunobiology. A review
S. Mukaratirwa and E. Gruys

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SUMMARY
Canine transmissible venereal tumour (CTVT) is the only known naturally occurring tumour that can
be transplanted as an allograft across major histocompatibility (MHC) barriers within the same
species, and even to other members of the canine family, such as foxes, coyotes and wolves. The
progression of this tumour is unique in that, it follows a predictable growth pattern. In natural and
experimental cases, the growth pattern includes progressive growth phase, static phase and regression
phase, and this is followed by transplantation immunity in immunocompetent adults, while metastasis
occurs in puppies and immunosuppressed dogs. Because of the uniqueness of CTVT transmission and
progression, experimental investigations of various aspects of the biology of CTVT have been used to
provide clues to the immunobiology of both animal and human tumours. This review examines the
current state of knowledge of the aspects of the cytogenetic origin, immunopheynotype,
immunobiology and immunotherapy of CTVT.
Keywords: Cytogenetic origin; Dog diseases; Genital neoplasms; Immunobiology; Immunophenotype;
Neoplasms; Transmissible venereal tumour.

INTRODUCTION
Canine transmissible venereal tumour (CTVT),
also known as canine transmissible sarcoma, is a
naturally occurring contagious round cell neoplasm
of dogs located mainly on the external genitalia of
both sexes. It is transplanted during coitus with
intact viable cells across MHC barriers, and even

to other members of the canine family, such as

foxes,

coyotes,

and jackals

(37).

Laboratory

transplantation of CTVT from one dog to another

using viable cells is also possible (91). Metastasis
of CTVT is uncommon, only occurring in puppies
and immunocompromised dogs. Most of the
reported metastasis cases actually are mechanical
extensions of growth or transplantation to skin,

allograft across MHC barriers, investigations of

various aspects of tumour biology (cytogenetics,
immunophenotype, immunology, immunotherapy,
radiotherapy and chemotherapy) have been done to
provide clues to similar phenomenon that occur in

other animal and human tumours. Thus, CTVT

has been studied extensively as a model of both
animal and human tumours.

A very interesting

aspect

that

has

attracted

attention of CTVT is the role of the host's immune

response during the progressive and regressive

stages of the tumour. Spontaneous and
experimentally transplanted CTVT shows an initial

stage of rapid tumour growth followed by a

cervix, uterus, and fallopian tubes from the

regressive stage that often completes in adult

animals. Several reasons supported by both in vitro

tumour at the external genitalia. However, distant

metastasis to the inguinal lymph nodes and brain

CTVT initially evades the immune system and

and in vivo studies have been proposed as to how

(3,30,74), adenohypophysis (53), and liver (89)

later succumb.

has been reported.

A review limited

The uniqueness of CTVT lies in the fact that this

is the only proven example of a naturally
occurring tumour that is transmitted as an allograft
by cell transplantation, and the tumour becomes
autonomous from the original host. In other
words, the tumour behaves like a parasite. This
kind of tumour develops only in the dog, probably
because during coitus there is extensive abrasions

clinico-pathological

and bleeding of the penile mucosa and vagina,

to the epidemiology and

features has already been

published (23). The aim of this paper is to review

the current knowledge of the cytogenetic origin,
immunophenotype, immunobiology and immuno-

therapy of CTVT, and

to

discuss how these

tumour characteristics are involved in the unique

behaviour of this tumour.

CYTOGENETIC ORIGIN

easy.

The normal diploid number of chromosomes in the

Because CTVT can be easily transplanted as an

somatic cell of the dog (Canis familiaris) is 78,

making

transplantation

of the tumour

103
Adams et al. (I), and Gonzales-Angulo and
Hernandex-Jauregui (32) found type-C viral
particles in tissue culture-grown CTVT tumour
cells. Cell-free transmission has been reported

and 76 of these, the autosomal chromosomes, are

acrocentric, while two, the sex chromosomes, are
metacentric (66). Cytogenetic studies on
spontaneous

and

experimentally

transplanted

(50), suggesting an infectious agent as a cause.

Contrary to these findings, Cockrill and Beasley,
and Hill et al., using ultrastructural techniques,
were unable to observe any viral-like particles
within the CTVT cells (18,38). However, they
observed lamellar arrays in CTVT resembling
structures described by Lombard and Cabanie
(50), and Amber et al. (7) as viral like-inclusion

CTVT have been done by several researchers in

different geographical areas of the world, and
these studies have demonstrated that tumours from
different geographical regions (France, Jamaica,
Japan, Kenya, Nigeria, Uganda, USSR, and USA)
have a similar karyotype in terms of chromosome
number (59 chromosomes), the frequency of

metacentric chromosomes and the incidence of

bodies. The presence of these viral like particles in

CTVT could be incidental findings. Up to now, no
virus has been isolated from CTVT cells.

marker chromosomes, and these are clearly

distinguishable from that of the normal canine cell

(2,8,31,44,47,52,63,84,86,88). The demonstration

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that the karyotypes of CTVTs from different

geographical regions are similar suggests that

summary, it is apparent from all these

investigations that no reproducible evidence is
In

CTVT is transferred from one animal to another

by transplantation of viable cells. The following
findings strongly support the cellular transmission
of CTVT and the idea that CTVT originated from

available to demonstrate viral aetiology of this

CTVT. In contrast, cytogenetic and immunological
(see below) studies strongly suggest that CTVT is
a
cell-transmitted neoplasm. However, the
etiologic agent that originally induced the CTVT is
still unknown.

one cell type:

1. CTVTs from different geographical regions

have the same number of chromosomes and
similar frequency of metacentric chromosomes
(2,8,31,44,47,52,63,84,86,88).
2. The number of chromosomes and the frequency
of metacentric chromosomes are maintained
after subsequent passages in vitro and in vivo

CTVT IMMUNOPHENOTYPE

(2).

tumour in the genitalia and the metastatic

tumour in the brain are identical (3).

4. Banding pattern analysis of CTVT chromosomes revealed extensive structural rearrangements in the CTVT, and these rearrangements

individual dogs from various regions contain

identical rearranged gene (c-MYC oncogene)
(5,17,48).

6. In a xenograft model of CTVT (XTVT) in

NOD/SCID mice, XTVT cells retained the
cytological and histological features of CTVT,
as well as characteristic rearranged LINE/
c-MYC junction (34,35). This constancy and
stability of CTVT karyotype might contribute to
the easy transplantability of this tumour.

The contagious nature of CTVT has led to

numerous attempts to demonstrate a causative
oncogenic viral agent. Some researchers have
demonstrated by electron microscopy virus like
particles within

some CTVT cells (7,49,50).

sections,

eosin-stained

and

progressive CTVT is characterized by compact

masses of neoplastic cells arranged in a diffuse
pattern and supported by thin trabeculae of
fibrovascular tissue. The tumour cells are round or
polyhedral with a large, round, central nucleus,
usually containing a single prominent nucleolus
(Figure 1). The cytoplasm is slightly granular,

3. The number of chromosomes of the primary

were identical in different tumours (66).

5. Southern blot analysis showed that CTVT from

haematoxylin-

In

vacuolated and eosinophilic with indistinct borders.

'

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)'..,r.,,N.,A.
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77 tc;`>:..,.

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4,,V, !.,7

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i.

kw

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4.
i

'011

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tlet
"'"V ''',.
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1`;',:et fa' . , et at
--t,''.

Figure 1. CTVT during progressive stage. The tumour

consists of sheets of polyhedral cells, with large, central
nucleus, containing a central nucleolus. H.E. x 200.

104
Because the histological features and ultrastructural

stem cell (54).

features of CTVT cells do not clarify the cell of

origin, CTVT originally has been described as a
lymphosarcoma, a tumour of neuro-ectodermal or

In summary, the phenotypic origin of CTVT is not

origin, a histiocytoma, an infective

granuloma or a round cell sarcoma (24,46,65, 80).
Most canine round cell tumours have been
immunocharacterized using several tumour
markers (25,29,58,81), making it easy for accurate
aortic

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diagnosis and classification. Although CTVT has

been subjected to immunohistochemical studies
with several tumour markers (Table 1), its origin
and the immunophenotype still remain uncertain.
However, immunohistochemical studies with a
panel of several antibodies have managed to rule
out some of the early suggestions.
Antibody specificity

Cellular specificity

Keratin

Epithelial cells

Vimentin

Mesenchymal cells

Desmin

Muscle cells

a-smooth muscle actin

Smooth muscle cells

CD3

T-Iymphocytes

IgG and IgM

B-Iymphocytes

X-light chains

B-Iymphocytes

K-light chains

B-lymphocytes

Lysozyme

Histiocytes

ACM1

Histiocytes

A-1-antitrypsin

Histiocytes

Result

Table 1. Antibodies and their cellular specificity used in

immunohistochemical characterization of CTVT
(Marchal et al. (54) and Mozos et al. (59)).

yet clear, but the expression of ACMI, lysozyme

and AAT suggest a histiocytic origin because these
antigens are not expressed by other mesenchymal
round cells, except those of hystiocytic origin (54,
73). Because there is no significant difference
between the immunophenotype of histiocytomas
and CTVT, the differential diagnosis should be
based on clinical and histopathologic criteria.

IMMUNOBIOLOGY; A MODEL FOR

TUMOUR IMMUNOLOGY
In clinical patients, CTVT grows rapidly after
sexual transmission, followed by indolent local
tumour growth or progression with metastasis:
some tumours regress spontaneously (72), and this
is followed by transplantation immunity (16). In
experimental cases, CTVT evades immunosurveillance and grows progressively for 12

weeks, until it becomes vulnerable and subject to

the host's anti-tumour immune response (43). In
immunocompromised animals and puppies, there is
metastasis (21). The frequent spontaneous

regression of both naturally and experimentally

transplanted CTVT suggests that the immune
response against the tumour plays a major role in
determining the course of the disease. CTVT
evokes both humoral and cell-mediated immune
response, and also transplantation immunity in
immunologically competent host, which prevents
subsequent tumours (28,57,68). Studies done on
aspects of the immune response, including the role
of tumour-associated antigens, humoral and
cell-mediated immunity, and MHC antigens are
mentioned below.

From the data shown in Table I, CTVT cells are

negative for keratins, a-smooth muscle actin,
desmin, CD3, immunoglobulins G and M, X-light
chains and X-light chains, and this means that an
epithelial, ' smooth muscle, and T- and B
lymphocyte origin can be ruled out. Antibodies
against CD3, surface immunoglobulins G and M,
X-light chains and X-light chains are useful for
differentiating CTVT from lymphomas and plasma
cell tumours. Lysozyme and alpha-anti-trypsin

(AAT) have been considered good markers for

benign and malignant histiocytes (79), and these
antigens are not expressed by other mesenchymal

cells (73). ACM1 is a canine specific antibody

recognizing a fixation resistance epitope present in

the majority of canine mononuclear phagocyte

CTVT associated-antigens and humoral

immunity
CTVT has been reported to be antigenic and to
evoke transplantation immunity in the host that

A tumour antigen
associated with CTVT has been identified and
rejected the tumour

(11).

partially characterized (68). The presence of this

tumour-associated antigen has been confirmed by
immunoelectron microscopic localization during
the progressive, steady and regressi;re stages by
using antibodies against

the tumour-associated

antigen (39). It has been shown that following

transplantation of CTVT, .this tumour-associated
antigen is shed into circulation during the
progressive stage (68). The amount of this antigen

105
in serum increased proportionately with tumour

volume, and the antigen could no longer be

detected in sera 48-72 hours after surgical removal
of the tumour (92). This suggests that this antigen
and its complexes may be responsible, at least
partially, for blocking the host's immune

mechanism as suggested in other tumours (13).

There is convincing evidence that humoral
immunity plays a role in CTVT progression.
Passive transfer of post-regression sera to

T-cell cytotoxicity is believed to be associated with

apoptosis (10) and apoptosis is increased in
regressing CTVTs (33).

ko 4
2'

tumour

development

if

O.

e0

Moreover, the growth of CTVT is inhibited in

puppies born to dams that are immunized with

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No
&

simultaneously with tumour transplantation (76).

associated antigens can be demonstrated (11,19).

Perez et al. (72) also found more B-lymphocytes

-0 0 0

administered

CTVT before or during pregnancy (91).

membraneantibodies against
Furthermore,

0."

0.Ir. p o e
,,4

04.

CTVT-bearing dogs was shown to inhibit and

prevent

eir v

IP

le

il

aEb

co

SO'

NIP
to

. 000* *4

.,

00)4
41

is

411.

_____4..

";;.,

4"4,

., c ee'e -V

-4

'

0,4

'

qP

tw

II

`.-

rt ;

74

ida

..?

Figure 2. CTVT during the early regression stage.

tumour

infiltrating

lymphocytes

(TILs)

intra- and peri-tumoral

inflammatory infiltrates of regressive tumours than

Numerous

of progressive tumours. Studies by Fenton and

Peripheral blood lymphocytes (PBL) of dogs in

which CTVT had regressed, have been shown to

and plasma

cells

in

Yang, showed that more CTVT cells have

membrane-bound antibodies in the steady and

regression states than in the progression state (28).

In addition, the presence of such antibodies in

adult dogs, but the absence in the puppies with
tumour metastasis (28), suggest the importance of
humoral immunity
tumour.

in the

progression of this

(arrows). H.E. x 400.

be cytotoxic to the tumour cells in contrast to PBL

of normal dogs and animals during progressive

tumour growth (20). In addition, sera of dogs in
which the CTVT had regressed could be
demonstrated to mediate antibody-dependent

cellular cytotoxicity (ADCC) with normal dog

lymphocytes or cytotoxic PBL as effector cells

In summary, it appears that membrane-associated

(20).

transplantation antigens are expressed on the

CTVT can be transplanted with intact viable cells

across MHC barriers within the species, and even

surface of CTVT cells. However, whether the

immune response towards these antigens plays a
role in the induction of spontaneous regression of
CTVT is not yet established. Because these

tumour-associated antigens are expressed during

the progressive, steady and regressive phases, they
are not likely to play an important role in the
spontaneous regression.

Cell mediated immunity and major

histocompatibility (MHC) antigens
Tumours are frequently infiltrated by T-lymphocytes and natural killer (NK) cells (15). Increased
numbers of tumour infiltrating lymphocytes
(TILs) (Figure 2), particularly T-lymphocytes,
are associated with tumour regression in CTVT
(43,57,85). Anti-tumour effects of TIL have been
intensively studied. In human renal cell carcinoma,
proliferating intratumoural CD8+ lymphocytes
indicated effective anti-tumour immunity (64). The

to other members of the canine family, such as

foxes, coyotes, and wolves. The effector functions
of both T-lymphocytes and natural killer (NK)

of MHC antigens
expressed on the surface of tumour cells. MHC
- antigens are membrane glycoproteins that display
peptide antigen to T-lymphocytes. MHC antigens
cells depend on the level

function as cell surface markers to signal cytotoxic

(MHC class I) and helper-T-lymphocytes (MHC
class II), and are indispensable for the presentation

of cells bearing "foreign" antigens to cytotoxic

T-lymphocytes (95). MHC class I antigens play a
key role in host defence against cells expressing
foreign

antigens.

Several

naturally

occurring

tumours and virally transformed cells show an

overall suppression of these surface antigens (27).
Since the MHC class I antigens are required in the
presentation of neoantigens on tumour cells to the
cytotoxic T-lymphocytes, their absence from the

106
cell

surface may lead to the escape of these

tumours from immunosurveillance. CTVT cells are

Progressive stage

not rejected as first set allograft. The reason for

this is still not clearly established. After 2 to 4

Static stage

Regression stage

!ILA-0

months of progressive growth, the tumour

regresses spontaneously in immunocompetent adult
dogs, or results in metastasis in puppies and
immunosuppressed adult dogs.
Blood vosool

The mechanisms of how the CTVT manage to

overcome MHC barriers so successfully for such a
long period and yet succumb later are not known.
Recent studies have demonstrated that CTVT cells
in the progressive stage lacked the expression of

both WIC class I and class II antigens, whereas

30 to 40% of the tumour cells in the regressive
stage expressed these antigens (72,90). Certain
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human

malignant

tumours,

including

eccrine

porocarcinomas (41), some skin tumours (40) and

cervical carcinomas (22), have markedly reduced
or non-detectable levels of MLIC class I antigens

Figure 3. Expression and modulation of MHC class I

antigens during CTVT progression and regression. On
transplantation, CTVT cells escape immunosurveillance
by down-regulation of MHC class I antigens, therefore
avoiding destruction by T-lymphocytes (CTLs), and
avoid natural killer cells by expression of ectopic nonclassical MHC antigens, such as HLA-G, and shed
tumour-associated antigens (TAAs) into the circulation.
This leads to tumour progression. During the static
stage, tumour-infiltrating lymphocytes (TILs) induce
tumour cells to express MHC class I antigens through
secretion of cytokines. During the regression phase,
CTVT cells expressing class I antigens are recognized

(in contrast to their benign and normal cellular

by CTLs leading to regression.

counterparts), suggesting a possible mechanism for

their escape from immune surveillance. In

Heat shock proteins (HSPs) may play a role in the

addition, transfections of functional MHC class I

antigens into highly tumorigenic adenovirustransformed cells, which originally failed to

re-expression of MHC antigens in CTVT. HSPs

are among the most abundant proteins in living
cells

and become even more abundant during

that the lack of expression of MHC class I antigens in the progressive stage may be responsible,
at least in part, for the 'universal uptake' and

stress. In cells, HSPs are actively associated with

antigen presentation (87), lytic activities of natural
killer cells (14), and cytotoxic T-lymphocytes (87).
Transfection of B16 melanoma cells with HSP 65
dramatically increases levels of class MHC

progressive growth of CTVT in allogenenic host.

antigens on their surface, and these transfected

The re-expression of MHC antigens in regressive

cells are effectively lysed by alloreactive cytotoxic

T-lymphocytes (87). In CTVT, increased levels of

express MHC class I antigens, abrogated the antigenicity of these cells (83). This strongly suggests

stage might be responsible for the spontaneous

regression of CTVT after a progressive growth.
The precise mechanism of how CTVT cells are
activated to re-express MHC antigens in the
regressive phase is yet to be confirmed. However,
several cancer cell lines

can be activated by

X-interferon to express MHC antigens (94). It has

been shown that co-culturing CTVT cells with

TILs or culturing with TILs-conditioned media
promote the expression of MHC classes I and II
antigens by CTVT cells (43). From these findings,
it is reasonable to assume that modulation of the
re-expression of MHC antigens is by soluble
factors or cytokines released by TILs (Figure 3).

HSP 60 in cells in the regression phase has been

observed (17), suggesting HSPs may play a role in
the regression.
Although

cytotoxic

T-lymphocytes

recognize

tumour-associated antigenic peptides presented by

MHC class I molecules, natural killer (NK) cells
are cytotoxic for tumour cells that have lost MHC
class I expression. The- loss of MHC class I may
activate

NK

cells

leading

to

tumour

cell

destruction (75). NK cells destroy infected and

malignant cells via two mechanisms: antibodydependent cellular cytotoxicity and killer-activating

and killer inhibitory receptors (12): The killerinhibitory receptors recognize MHC class I

This may underline the efficacy of interferon in

the treatment of CTVT and other malignancies.
Greater understanding of the cytokines or growth
factors produced by TILs could lead to novel

destroyed. Thus, in absence of MHC class

therapeutic regimens for treating tumours.

molecules, as in CTVT cells in the progression

molecules. This recognition overrides the effector

function of NK cells and the target cell is not

I

107
stage,

an

inhibitory signal

from

the

killer-

parenchyma by fibrovascular stroma (Figure 4).

inhibitory receptor is not generated and the NK

cell should kill the abnormal cells. In fact NK cells
are cells specialized in killing cells that no longer
express MHC class I antigens. The mechanism of

how CTVT cells escape immunosurveillance by

NK cells is not clear. Some tumours like
melanoma cells express ectopic non-classical MHC
class I, such as HLA-G (70,71), which may block

.....

lie

I'

..

"4

'''

I and Class II antigens on cells in the

progressive stage of the tumour (90).

2. Expression of ectopic non-classical

MHC

antigens, such as HLA-G to escape NK cell

immunosurveillance.
3. Shedding of tumour-associated antigen (68).
4. Formation of immune complexes (69).

5. Production of blocking factors (11) to escape

recognition and to block the hosts' immune

it

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e \

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t It \
,

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.--

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,4

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tio.' :
.

at
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4,... ..6 .
..

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P..04

Class

.1
li.

t
i

4,3

in the progressive phase CTVT utilise to avoid NK

activity.

undergone immunoselection processes, which has

resulted in its ability to escape from host's immune
surveillance. The following factors may play a role
(see Figure 3):
1. Lack of expression or down regulation of MHC

('%,
'47,0.1lia:
t.,_ 4 Le .11 v i
,..._, ,.

,.
r

successfully for a long period and yet succumb

later are not clear. It seems as if CTVT has

Ar

the activating functions of NK cells (4). Further

research is needed for the mechanism that CTVT

In conclusion, the mechanisms of how CTVT cells

manage to overcome histocompatibility barriers so

Downloaded by [180.254.211.128] at 05:09 07 April 2016

- .." nr I.

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#,

,A,i
I

' le. Ot *"0

se A
:r. to,.
CP
es

es:# 5

jiZdq

ArVIP

ZZAk

Figure 4. CTVT during the regressive stage. Collapse

of the tumour parenchyma and replacement by fibrovascular stroma. H.E. x 200.

The stromal cell type and extracellular matrix

components of the progressing and regressing
tumours have not been investigated. Different
ECM components may accumulate during different
stages of the tumours (like in malignant vs benign

tumours) in some human (45) and canine (61)

tumours. No studies have analyzed the temporal
expression of extracellular matrix components like

tenascin, hyaluronan and versican that play an

important role in tumour progression in some
human (78) and canine tumours (26,60).

system.

IMMUNOTHERAPY

EVALUATION OF CTVT STAGE

Immunotherapy

CTVT responds well to chemotherapy using

cyclophosphamide, methotrexate, or vincristine

alternative or adjuvant approach to the treatment of

many malignancies. The potential for immune
modulation as a treatment of tumours is a focus of
cancer researchers throughout the world. Efficient
chemotherapy protocols for CTVT are known, but
there is little information on the presence of both
an efficient prophylactic approach to prevent
CTVT and immunotherapeutic agents effective
against CTVT. Cell-mediated immunity accompanies chemotherapy-associated regression in CTVT
(33). Immunostimulators (paramunity activators)

(6). Treatment could be more properly selected if

the stage of growth is determined. Besides clinical
observation and monitoring, evaluation of the

growth stage of CTVT may be very difficult.

Assessment of proliferative and apoptotic fractions
of CTVT has shown that during tumour

regression, tumour cell proliferation ceased and

apoptosis increased (33).

TILs are increased

during the regression phase of CTVT (72), and

therefore, quantitation of TILs may be used to
determine the stage of CTVT. Since MHC
antigens (72) and heat shock proteins (17) are
increased during regression of CTVT, these may

also be used to evaluate the stage of growth.

During the regressive stage, there is collapse of
the tumour and replacement of the tumour

is

receiving

interest

as

an

have been tried in several tumours and some of

them have produced positive results (9, 62).
Paramunity activators are given with the intention
of enhancing the non-specific immune reactivity to

the host, and this non-specific immunity is both

humoral and cellular (55). Since humoral and
cellular immunity are known to play an important

108
role

in

the

regression

of CTVT (20,56),

paramunity activators are expected to be effective

in both prophylaxis and treatment of this tumour.
Very few paramunity activators have been tried on
CTVT. Immunotherapy studies with bacillus

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