Role of cell based approaches in cancer immunotherapy

An integrated immune system prevents development and progression of neoplastic cells in a process termed as immune surveillance. T-cells play an important role in detecting and eliminating tumor cells. In turn, they are dependent on dendritic cells for tumor antigen presentation and activation signals to stimulate them. One of the most important reasons behind failure of cancer immunosurveillance is hampered T-cell activity due to lack of co-stimulatory activation signals by dendritic cells resulting into peripheral tolerance. Other factors driving tumor progression include immunosuppressive tumor micro-environment, infiltration of regulatory T cells, release of immunosuppressive cytokines like IL-10 and TGF-β, reduced expression of MHC molecules, myeloid derived suppressor cells (MDSCs) and heterogeneity of tumor sub-clones at the genetic level. Studies have shown that expansion of Treg cells is associated with poor prognosis and reduced survival. Similarly, abnormal accumulation of MDSCs is also correlated with tumor evasion mechanism. Though, chemotherapy is first line of treatment, the efficacy is restricted later due to development of drug resistance. The major reasons for resistance development includes drug-targeted gene amplification (e.g. BRAF gene) and substitution mutation in some cancer cells leading to the escape of drug cytotoxic effect.1 Further, non-specific cytotoxicity of chemo agents result into lymphodepliton. To address all these issues, new therapeutic interventions are required which alone or in combination alter the tumor microenvironment to enhance beneficial effects without causing toxicity. In this context, immunotherapy is expected to play significant role. Cancer immunotherapy can be defined as set of techniques aimed to eliminate malignant tumors through mechanisms involving immune system responses. The agents driving immune alteration are termed as immunomodulators. In this review, we will discuss briefly some of specific methods mediating immunomodulation including dendritic cell based approaches, adoptive T cells transfer and mesenchymal stem cells based targeted delivery of drugs.