Cancer cells within a population are heterogeneous due to genomic mutations or epigenetic changes. The immune response to cancer especially the T cell repertoire within the cancer microenvionment is important to the control and growth of cancer cells. When a cancer clone breaks through the surveillance of the immune system, it wins the battle to overcome the host’s immune system. In this review, the complicated profile of the cancer microenvironment is emphasized. The molecular evidence of immune responses to cancer has been recently established. Based on these molecular mechanisms of immune interactions with cancer, clinical trials based on checkpoint inhibition therapy against CTLA-4 and/or PD-1 versus PD-L1 have been successful in the treatment of melanoma, lung cancer and other types of cancer. The diversity of the T cell repertoire is described and the tumor infiltrating lymphocytes within the cancer may be expanded ex vivo and infused back to the patient as a treatment modality for adoptive immunotherapy.© 2024. The Author(s).