IMMUNITY IN TUMOR TRANSPLANTATION 419 



weakened tumor pieces, a second non- weakened piece was inoculated, there 

 occurred on the second and on the third day a marked accumulation of lympho- 

 cytes, the sarcoma cells disappeared rapidly, fibrous tissue formed subsequent- 

 ly, and also plasma cells were seen. With the disappearance of the sarcomatous 

 tissue the lymphocytic reaction came to a standstill. 



However, preceding these latter investigations Da Fano, in 1910, had 

 emphasized the significance of lymphocytes and plasma cells in tumor im- 

 munity, but his interpretation of the function of the lymphocytes differed 

 from that of Tyzzer and also from our conception. Da Fano noted an ac- 

 cumulation of lymphocytes not only around transplanted pieces of tumor, but 

 these cells as well as plasma cells were seen also in various other places as for 

 instance in the connective tissue underneath the skin of the animal during the 

 process of immunization. Only living tumor tissue elicited this reaction; 

 furthermore, it was lacking around a second piece of tumor inoculated in an 

 animal in which immunity had already developed. Da Fano attributed, there- 

 fore, to the lymphocytes and plasma cells the function of initiating the general 

 state of immunity which follows the inoculation of a piece of homoiogenous 

 normal tissue or tumor. Somewhat later, Baeslack observed in addition to the 

 localized reaction, a general reaction of the lymphocytes to tumor growth ; 

 the active growth of a homoiogenous tumor was accompanied by a decrease 

 in the number of lymphocytes and by an increase in the number of poly- 

 morphonuclear leucocytes, whereas the retrogression of a tumor was associ- 

 ated with an increase in the number of lymphocytes as an indication of the 

 development of immunity against the transplanted tumor. Quite recently, 

 Lewis has confirmed the increase in the number of polymorphonuclear leuco- 

 cytes in the peripheral circulation in mice in which the transplanted tumor 

 grows. 



The most extensive and ingeniously varied investigations concerning the 

 relations between tumor immunity and activity of lymphocytes were carried 

 out by Murphy and his associates. They noted both a local accumulation of 

 lymphocytes around the tumor graft as well as a general increase of lympho- 

 cytes in the circulation following transplantation; an injurious effect re- 

 sulted, however, from an increase in the number and activity of lymphocytes, 

 not only in homoiogenous and heterogenous, but also in autogenous tumor 

 grafts. After heterotransplantation of a piece of tumor, the lymphocytic re- 

 action played the principal role in the destruction of the transplant. These 

 investigators concluded, furthermore, that immunity against a tumor can be 

 elicited not only through inoculation with a piece of tissue or of tumor be- 

 longing to the same species, but that any non-specific agency which increases 

 the number and activity of lymphocytes, increases thereby the defensive reac- 

 tions of the host against the transplant, and conversely, any agency that de- 

 creases the number and activity of lymphocytes increases thereby the sus- 

 ceptibility of the host to the tumor transplants. Small doses of Roentgen rays 

 stimulate and strong doses injure the lymphocytes ; exposure of mice to 

 graded intensities of dry heat and injections of certain oils or unsaturated 

 fatty acids stimulate the lymphocytes. The effects of these various agencies on 



