TUMOR PROGRESSION BY LUNG CANCERS GROWING IN HOSTS OF DIFFERENT IMMUNOCOMPETENCE

Background - Although much study has been devoted to factors that modu late the first (carcinogenesis) and third (metastagenesis) stages of t umor progression in vivo, little is known about factors that modulate the second (progressive de-differentiation) stage of tumor progression in vivo. Methods - Twenty primary and two metastatic non-small cell h amster lung cancers that closely resembled their human counterparts we re concomitantly propagated in 39 normal and 218 transiently immunosup pressed hamsters, and in 71 immunoparetic nude mice of two kinds. Hist ological patterns between donor tumors and immediate recipient tumors were compared. Results - The sequential cellular changes (phenotypical de-differentiation) that are considered typical of tumor progression during continued cancer growth in the original host were noted in a ma jority (48/81; 59%) of the tumor transplant recipients whose immunocom petence was equal to or greater than that of the tumor donor, Similar changes occurred in only a small minority (10/74; 13.5%) of tumor tran splant recipients whose immunocompetence was less than that of the tum or donor (p<0.001). Histological patterns of tumor re-growth in the sa me animal after near-total tumor resection showed continuing de-differ entiation in 11/19 (58%) normally immunocompetent tumor hosts, but in only 15/109 (13.7%) immunologically impaired tumor hosts (p<0.025). Co nclusions - These studies show a previously undescribed immune respons e-related modulating influence upon classic tumor progression in vivo; the rate and degree of de-differentiation during tumor progression is directly related to the level of host immunocompetence. Immunodepress ion favors maintenance of the differentiated state, but normal or elev ated immunoreactivity is associated with progressive de-differentiatio n.