Cytokine Dysregulation in Invasive Cervical Carcinoma and Other Human Neoplasias: Time to Consider the TH1/TH2 Paradigm

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Abstract
Tumor immunology has evolved in parallel with the immunology of infectious diseases and has attempted to reproduce the successes obtained in the prevention and cure of infections by directing the immune system to attack tumor antigens. However, this objective has not yet been reached. The lack of success has been analyzed in depth and mainly attributed to the fact that neoplastic cells may be weakly immunogenic. Failure has led to questioning the importance of tumor-specific immune responses in controlling disease progression and has raised doubts about the value of immune response-based therapy in clinical oncology. Tumor-specific immune responses are nevertheless evident in tumor-bearing patients as shown by the following observations: 1) The tumor mass is frequently infiltrated with mononuclear cells; 2) tumor-specific cytotoxic T lymphocytes (CTLs) are present in patients with cancer, as are natural killer (NK) cells; and 3) an altered pattern of expression of major histocompatibility complex (MHC) class I and class II molecules is observed on the surface of tumor cells [reviewed in (1)]. Numerous mechanisms have been postulated in an attempt to understand the failure of the immune system to control and/or impede tumor growth. These mechanisms include the following possibilities: 1) Some tumors could be poorly immunogenic, and/or MHC expression could be down-regulated; 2) antitumor immunity could select immune response-resistant tumor cells; 3) antigens can be shed by the tumor, bind to tumor-specific lymphocytes, and prevent the recognition of tumors by such lymphocytes; and 4) tumor cells could be tolerogenic either because they do not express costimulatory molecules or because they do not produce cytokines [reviewed in (1)].