Development of Personalized Combination Cancer Immunotherapy Based on the Patients’ Immune Status
Cancer immunotherapies, particularly immune-checkpoint blockade and T cell-based adoptive cell therapy, have recently been recognized as cancer treatments that show strong and durable responses even for advanced cancer patients with multiple metastases. The major issues in the development of cancer immunotherapy are the identification of biomarkers to distinguish responders and non-responders, and the improvement of efficacy of immunotherapy possibly by combination with appropriate immune interventions targeting different key regulating points in the anti-tumor immune responses. Interestingly, pretreatment T cell immune status varies among cancer patients, and appears to correlate with responses to various cancer treatments including surgery, chemotherapy, radiation therapy, and immunotherapy. Balance of anti-tumor T cell induction pathway and immunosuppressive pathway, which are regulated by characteristics of both cancer cells and patients’ immune reactivity, may define the differential immune status among cancer patients along with environmental factors such as intestinal microbiota. The analysis of such mechanisms may lead to the identification of immune biomarkers and immune-modulating strategies for combination immunotherapies. Further research on human cancer immunopathology will lead to the development of effective personalized combination immunotherapies based on the evaluation of cancer patients’ immune status.
KeywordsCancer immunotherapy Cancer immunopathology Biomarkers Combination immunotherapy Personalized therapy
These studies were supported by Grants-in-Aid for Scientific Research (23240128, 26221005) from the Japan Society for Promotion of Science, a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a Grant-in-Aid for Cancer Research (23-A-22, 19–14) from the Ministry of Health, Labour, and Welfare, Japan. We also thank Ms. Misako Sakamoto and Ms. Ryoko Suzuki for technical support and editorial assistance.
- Kawakami Y, Yaguchi T, Sumimoto H et al (2013a) Roles of signaling pathways in cancer cells and immune cells in generation of immunosuppressive tumor-associated microenvironments. In: Shurin M, Malyguine A, Umansky V (eds) Tumor immunoenvironment. Dordrecht/Heidelberg/New York/LondonGoogle Scholar
- Taube JM, Anders RA, Young GD et al (2014) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4:127Google Scholar
- Udagawa M, Kudo-Saito C, Hasegawa G et al (2006) Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and Bacillus Calmette-Guerin cell wall skeleton stimulation. Clin Cancer Res 12:7465–7475CrossRefPubMedGoogle Scholar