| Year | Event |
| 1868 | First report of an intentional infection of a cancer patient with erysipelas by Wilhelm Busch, with notable shrinkage of the tumor11 |
| 1883 | Elie Metchnikoff publishes a key paper describing phagocytic cells(macrophages) in frogs102; awarded Nobel Prize in 1908 |
| 1890 | Discovery of antibodies(diphtheria and tetanus) by Emil von Behring and Kitasato Shibasaburō103; Nobel Prize awarded to von Behring in 1901 |
| 1891 | William Coley injected his first of many cancer patients with bacteria, reporting tumor regressions in many of them14 |
| 1895 | Discovery of complement, by Jules Bordet104; awarded Nobel Prize 1919 |
| 1897-1901 | Paul Ehrlich “Side-chain” theory of antibody specificity(adaptive immunity, autoimmunity)105; awarded Nobel Prize in 1908 |
| 1901 | Serological discovery of blood groups, by Karl Landsteiner106; awarded Nobel Prize in 1930 |
| 1901-08 | Rejection of transplanted tumors in mice, reported by Carl Jensen & Leo Loeb107,108 |
| 1914 | Genetic basis for the rejection of transplantable tumors, reported by Clarence Little109 |
| 1909-20 | Establishment of inbred strains of mice by Leonell Strong and Clarence Little110 |
| 1948 | First report of histocompatibility antigens being the basis for transplant rejection, by P. Gorer, S. Lyman, & G. Snell111. 1908 Nobel Prize awarded jointly to G. Snell,B. Benacerraf, & J. Dausset in 1980 |
| 1955 | Natural-Selection Theory of Antibody Formation, first formulated by N. Jerne112; awarded Nobel Prize in 1984 |
| 1956 | Discovery of acquired immunological tolerance by R. Billingham, L. Brent & P.Medawar. Nobel Prize awarded to Medawar & F. Burnet in 1960113,114 |
| 1957 | Immune rejection of transplanted syngeneic tumors(i.e., each tumor is antigenically unique)115. Reported by Richmond Prehn & Joan Main. |
| 1957 | Interferon discovered, described as a factor that conferred the property of viral interference116, reported by Alick Isaacs and Jean Lindenmann. Its anti-leukemic effect is reported in 1984. |
| 1959 | Immune surveillance of cancer theory by Lewis Thomas & F. Macfarlane Burnet30–32 |
| 1959 | Chemical structure of antibodies, by Gerald Edelmann & Rodney Porter117–120; Nobel Prize awarded to both in 1972. |
| 1959 | BCG shown to have anti-tumor effects in a mouse model, reported by Lloyd Old, Donald Clark, & Baruj Benacerraf18 |
| 1973 | First description of dendritic cells, by Ralph Steinman & Zanvil Cohn121; Steinman awarded Nobel Prize in 2011 for discovery of the dendritic cell and its role in adaptive immunity |
| 1974 | First reports of the specificity of cell-mediated immunity by Peter Doherty and Rolf Zinkernagel122,123; Nobel Prize awarded to both in 1996 |
| 1975 | Monoclonal antibodies manufactured by George Koehler & Caesar Milstein124,125; Nobel Prize awarded to Koehler, Milstein & N. Jerne(for his theoretical contributions) in 1984 |
| 1975 | Discovery of tumor necrosis factor, reported by Lloyd Old, with Elizabeth Carswell, Robert Kassel, S. Green, N. Fiore, & B. Williamson19 |
| 1975 | First description of NK cells on a functional basis according to their ability to lyse tumor cells in the absence of prior stimulation126. Reported by Ronald Herberman, Myrthel Nunn, Howard Holden, & David H. Lavrin. |
| 1976 | Discovery of the genetic principle for generation of antibody diversity, by Susumu Tonegawa127,128; awarded Nobel Prize in 1987. |
| 1982 | Discovery of the T-cell receptor in 1982, reported by James Allison, B. McIntyre, & D. Bloch101 |
| 1984 | First report of interferon response in patients with hairy cell leukemia129 |
| 1991 | First report of a human tumor antigen recognized by T-cells, reported by Pierre van der Bruggen, C. Traversari, P. Chomez, et al.36 |
| 1996 | Discovery that CTLA-4 blocking antibodies could treat tumors in animal models, reported by Dana Leach, Matthew Krummel & James Allison72 |
| 1998 | Discoveries regarding the activation of innate immunity, by R. Medzhitov, P. Preston-Hurlburt, C. Janeway; & B. Beutler; Beutler awarded Nobel Prize in 2011130,131 |
| 2001 | Rag2 -/-immunodeficient mice, with no B or T cells, show increased susceptibility to spontaneous and carcinogen-induced tumors, reported by V. Shankaran, with L.J. Old, R. Schreiber, et al.132 |
| 2005 | Memory T-cells in colorectal tumors shown to predict clinical outcome, reported by F. Pagès, A. Berger, M. Camus et al.133 |
| 2010 | First autologous cell-based cancer vaccine (sipuleucel-T) is approved by the FDA for the treatment of metastatic, asymptomatic stage IV prostate cancer43,134 |
| 2010 | First successful use of gene-edited T-cells for the treatment of CD19+ hematologic malignancies in humans, reported by W. Qasim, H. Zhan, S. Samarasinghe et al.135 |
| 2011 | Anti-CTLA-4(ipilimumab), is the first inhibitory checkpoint inhibitor(ICI) approved by the FDA for treatment of stage IV melanoma136 |
| 2012 | Discovery of the CRISPR/Cas9 system, a simpler and more efficient method of genome editing, reported byJ.A. Doudna & E. Charpentier, with M. Jinek, K. Chylinski, I. Fonfara, & M. Hauer49 |
| 2013 | First use of CRISPR/Cas9 technique in eukaryotic cells, reported by F. Zhang, with L. Cong, F. Ran, D. Cox, S. Lin, R. Barretto, N. Habib, P. Hsu, X. Wu, W. Jiang, & L. Marraffini50 |
| 2016 | A second class of ICIs, anti-PD-1(pembrolizumab), is approved for the treatment of melanoma137 |
| 2016 | First characterization of the role of dendritic cell CTLA-4 in Th-1 immunity, reported by M. Halpert, V.Konduri, D. Liang et al.138 |
| 2016 | A third class of ICIs, PD-L1(atezolizumab), is approved for treatment of bladder cancer139 |
| 2016 | First test in humans of CRISPR gene-editing technique for CAR T-cell therapy51 |
| 2017 | Phase I/IIa study of an inhibitor of indoleamine 2,3-dioxygenase(IDO1), a non-membrane-attached enzyme with a checkpoint inhibitor function, shows promise95 |
cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead- Mohamed S. Aziz