Autologous tumor cell vaccines for post-operative active-specific immunotherapy of colorectal carcinoma: long-term patient survival and mechanism of function.
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Surgery remains the primary curative treatment but nearly 50% of patients relapse as consequence of micrometastatic or minimal residual disease (MRD) at the time of surgery. Spontaneous T-cell-mediated immune responses to CRC tumor-associated antigens (TAAs) in tumor-draining lymph nodes and in the bone marrow (BM) lead to infiltration of the tumors by lymphocytes. Certain types of such tumor-infiltrating lymphocytes (TILs) have a positive and others a negative impact on the patients' prognosis. This review focuses on advances in CRC active-specific immunotherapy (ASI), in particular on results from randomized controlled clinical studies employing therapeutic autologous tumor cell vaccines. The observed improvement of long-term survival is explained by activation and mobilization of a pre-existing repertoire of tumor-reactive memory T cells which, according to recent discoveries, reside in distinct niches of patients' bone marrow in neighborhood with hematopoietic (HSC) and mesenchymal (MSC) stem cells. Interestingly, memory T cells also contain a subset of stem memory T cells (SMTs) in addition to effector (EMTs) and central memory T cells (CMTs). The mechanism of function of a therapeutic vaccine in a chronic disease is distinct from that of prophylactic vaccines which have to generate de novo protective immune responses. The advantage of autologous vaccines for mobilization of a broad and highly individual repertoire of memory T cells will be discussed.
German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Volker
V
Schirrmacher
Philippe
P
Fournier
Peter
P
Schlag
D019496:Cancer Vaccines / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines