IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org

IOSR Journal of Pharmacy

Vol. 2, Issue 1, Jan-Feb.2012, pp. 074-075

IOSR

Theories of Immunosurveillance/Immunoevasion: An attempt
to explain Persistence of Cancer

Kirtimaan Syal* and Dibyajyoti Banerjee

Department of Experimental Medicine and Biotechnology,
Post Graduate Institute of Medical Education and Research, Chandigarh 160 012

Immunosurveillance theory advocates that cancer frequently arises in the body, recognized as foreign and eliminated by the
immune system. It was first conceptualized by Paul Ehrlich in 1900s. After around 50 years, Lewis Thomas laid the building
block of immunosurveillance by hypothesizing that cell mediated branch of immune system has evolved to locate cancerous
cells and kill them. In 1950s and early 1960, it has been realized that the immune system could recognize and respond to
tumor-associated antigens 1 . Thus, supporting the theory of immunosurveillance.

But if there is a surveillance system than why does cancer exist???

In 1974, it has been reported that nude mice do not demonstrate an increase in tumor incidence thus contradicting the
hypothesis of tumor immunosurveillance 2 . However, subsequent observations that nude mice do not completely lack
functional T cells and those two components of the immune system IFNg and perforin help to prevent tumour formation in
mice have led to renewed interest in a tumour-suppressor role for the immune response 3 " 4 . Many scientists believe that cancer
occurs because of the lack of these surveillance mechanisms and immunoevasion have no role to play. But, recent research
reveals about the potential of cancerous cells in evading immune system via mechanisms of immunoevasion. So there are two
possible ways via which cancerous cells can be persistent in the human body, one describes the inability of our immune
system to respond well to these cancer cells (due to defect in immunity/immunosurveillance) and the other possibility
advocates the evasion of immune cells by cancer cells (i.e. immunoevasion).

Defects in immunosurveillance mechanisms involves defective T cell anergy, the existence of more number of regulatory T
cells, systemic defects of dendritic cells derived from tumor patients, secretion of immunosuppressive cytokines, resistance to
apoptosis, and deficient expression of immunomodulatory molecules. Immunoevasion mechanisms include masking of
MHCs and lack of co- stimulatory signals.

Patients who have undergone transplantation take immunosuppressive drugs. Increased incidence of skin cancer and
lymphomas in such patients well demonstrates the role of immunosurveillance. In older patients and long surviving grafts,
44% cases of skin cancer and 14% of other cancer have been reported 5 . On the other hand, capacity of cancer cells to hide
the MHCs on their confrontation with immune cell, demonstrate the mechanism of immunoevasion.

Schreiber group reported the increase in incidence of chemically induced tumors having defective P53 suppressor gene, due
to which they are resistant to apoptosis4. Mark Smyth group illustrated the perforin mediated killing as an important
mechanism in tumor immunity 6 " 7 . Recently number of endogenous molecules that are hypothesized to be produced by cancer
cells and acting as the ligand of toll like receptor, have been reported to be contaminated by Pathogen associated microbial
pattern molecules which are acting as an artifact, thus supporting the theory of immune surveillance. On the other hand,
change in the level of growth receptors and omission of the receptors complementary to immune cells supports the hypothesis
of immunoevasion.

AIDS, the condition in which T helper cells count goes below 200 and patient become susceptible to various malignancies
like Kaposi sarcoma and cervical cancer illustrates the significance of immunosurveillance. In humans, there are 100 trillion
cells which include more than 1000 different types. But still very low frequency of cancer is observed. Why??? It could be
explained on the basis of immunosurveillance.

Further genetic susceptibility for cancer describes the inbuilt genetic defects in surveillance. Thus, explaining the persistence
of cancer cells to be dependent on defects in immuno surveillance. Tumor patients with higher titre of tumor infiltrating
lymphocytes showed a survival rate of 38% as compared to only 4.5% for patients lacking tumor infiltrating lymphocytes 8 . It
has been shown that people having large number of tumor infiltrating lymphocytes have significantly lower incidence of
metastasis. Based on this concept, adoptive immunotherapy has been supervised.

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IOSR Journal of Pharmacy

Vol. 2, Issue 1, Jan-Feb.2012, pp. 074-075

IOSR

One of the other important phenomenons is spontaneous resolution. Tumor occurs but in most of the cases they are cured
themselves. Clinical evidences related to self curing of hepatoblastomas and retinoblastomas are well illustrated 9 " 10 . And the
count of self curing in tumors is very large. In fact most of the cases of spontaneous resolution are never accessible to
clinicians.

But, many reports suggest the masking of tumor specific antigens and tumor associated antigens on confrontation with the
immune cell. Tumor cells produce cytokines and receptors essential for replication and spread. These facts strongly advocate
the theory of tumor evasion.

We can conclude that both tumor surveillance and tumor evasion are essential for persistence of cancer. Initially, scientific
community advocated immunosurveillance, but now research supports immunoevasion as well.

References:

1. Old LJ, Boyse EA. Immunology of Experimental Tumors. Annu Rev Med. 1964; 15: 167-186.

2. Stutman O. Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice.
Science. Feb 8 1974;183(124):534-536.

3. Shankaran V, Ikeda H, Bruce AT, et al. IFNgamma and lymphocytes prevent primary tumour development
and shape tumour immunogenicity. Nature. Apr 26 2001;410(6832):1 107-1111.

4. Kaplan DH, Shankaran V, Dighe AS, et al. Demonstration of an interferon gamma-dependent tumor
surveillance system in immunocompetent mice. Proc Natl Acad Sci USA. Jun 23 1998;95(13):7556-7561.

5. MacLeod AM, Catto GR. Cancer after transplantation. BMJ. Jul 2 1988;297(6640):4-5.

6. van den Broek ME, Kagi D, Ossendorp F, et al. Decreased tumor surveillance in perforin -deficient mice. J
Exp Med. Nov 1 1996;184(5):1781-1790.

7. Street SE, Trapani JA, MacGregor D, Smyth MJ. Suppression of lymphoma and epithelial malignancies
effected by interferon gamma. J Exp Med. Jul 1 2002;196(1):129-134.

8. Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T Cells, Recurrence, and Survival in Epithelial
Ovarian Cancer. New England Journal of Medicine. 2003;348(3):203-213.

9. Abbey AM, Flores RM. Spontaneous resolution of a pericardial cyst. Ann Thorac Cardiovasc Surg. Aug
2010;16(l):55-56.

10. McPherson T, Ogg G. Spontaneous resolution of basal cell carcinoma in naevoid basal cell carcinoma
syndrome/Gorlin's syndrome. Clin Exp Dermatol. Dec 2009;34(8):e884-885.

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