During the initiation, promotion, and progression of multi-step carcinogenesis, changes in specific host immunological factors have been observed. Although immunology of oral cancer has long been focused on antigens and lymphocytes, the fact remains that the antigen presenting cells, like the Langerhans cells (LCs) of the epithelium are initiators and modulators of the immune response. LCs as sentinels of immune response, have been investigated in several oral mucosal diseases, including cancer. Inadequate presentation of tumor antigens by host dendritic cells is one potential mechanism that allows tumor progression. In this review, the role of LCs in OSCC is discussed. Elucidation of the role of APCs, in particular LCs, may help to better understand the mechanisms underlying anti-tumour immune responses and, improve the effectiveness of anti-cancer immunity in tumour-bearing hosts. This section focuses on the roles LCs in the immunity of cancer and how cancer bypasses the dendritic cell-mediated immune responses, are discussed. Subsequently, the effects of tumor microenviornment on LC’s and their therapeutic implications are elaborated. During the initiation, promotion, and progression of multi-step carcinogenesis, changes in specific host immunological factors have been observed. Changes immunological of oral cancer has long been focused on antigens and lymphocytes, the fact remains that the antigen presenting cells, like the Langerhans cells (LCs) of the epithelium are initiators and modulators of the immune response. LCs as sentinels of immune response, have been investigated in several oral mucosal diseases, including cancer. Inadequate presentation of tumor antigens by host dendritic cells is one potential mechanism that allows tumor progression. In this review, the role of LCs in OSCC is discussed. Elucidation of the role of APCs, in particular LCs, may help to better understand the mechanisms underlying anti-tumor immune responses and, improve the effectiveness of anti-cancer immunity in tumour-bearing hosts. This section focuses on the roles LCs in the immunity of cancer and how cancer bypasses the dendritic ce ll-mediated immune responses, are discussed. The effects of tumor microenviornment on LC’s and their therapeutic implications are elaborated.