A RETROSPECTIVE VISION OF TUMOR IMMUNOLOG Y

The story of tumor immunology includes periods of hope followed by one s of disenchantment as far as clinical applications are concerned. In antiguity, cancer was considered ''contrary to Nature'', a concept whi ch was confirmed by Ehrlich at the beginning of our century when he la yed down the foundations of immunology. The latter was defined as the defence against all ''non-self'' intruders, including cancer, as oppos ed to the protection of ''self''. This concept was further accentuated by the theory of immunesur-veillance proposed by Burnet in 1969 which implicated a destruction of nascent neoplastic cells by T lymphocytes . To increase host defence was the basis of tumor immunotherapy with B CG, levamisol and other adjuvants. The appearance of the nude mouse, a thymic, and yet free of spontaneous tumors, led to a new paradigm, the network theory proposed by Jerne. This was based on immunological hom eostasis implicating that both ''self'' and ''non-self'' can be reject ed and tolerated. Cancer gradually ceased to be considered as ''contra ry to Nature''. As for the proposed viral etiology of cancer which was the basis of the National Cancer Act signed by Nixon in 1971, this le d to various breakthroughs and Nobel Prizes (Table 1), to discoveries such as reverse transcriptase, cellular oncogenes, tumor suppressor ge nes, which gave a new explanation for neoplastic transformation. The l atter can now be considered as the consequence of a cascade of molecul ar events which include oncogene expression, anti-oncogene deletion, e tc.. converting, step by step, for instance, a polyp into a colon canc er and its metastases. The availability of monoclonal antibodies capab le of attacking tumor cells did not lead to the expected success becau se of the complexity of the immune system. Attempts at a better unders tanding of the latter have led to a subdivision of the T lymphocyte CD 4 population into Th1 and Th2. Th1 favor rejection (tumoral, fetal or of transplants) through the elaboration of IL-2, IFN and. TNF while Th 2 lead to tolerance or acceptation through the production of IL-4, IL- 5 and IL-10: both functions neutralize each other establishing a ''nor mal'' equilibrium Th1 vs Th2. This could explain the state of ''tumor dormancy'' or tumors in situ which are apparently quite frequent. That any immunological stimulation would cause these dormant tumors to pro liferate is the basis of the immunostimulation theory proposed by Preh n and supported by the clinical observations of Stewart. This new conc ept has led some authors to propose that instead of destroying the tum or cells an attempt be made to maintain them in a state of dormancy in congenial company with normal cells.