Analysis of thymic structure in k-ras induced lung cancer murine model

INTRODUCTION The thymus is one of the primary lymphoid organs. It is responsible for the competence of the immune system together with its proper functioning. The hyperactivity of the thymus characterizes pediatric ages, and after puberty it undergoes involution. Very little is known regarding its possible alterations and related consequences in post-puberty ages, especially when looking into the context of neoplastic disease. In fact, with the advent of immunotherapy, the role of the immune system in counteracting tumoral state and progression has been highlighted. The aim of the current study is to understand the relationship between lung cancer and possible alterations in the thymic structure and to search for potential correlations between thymus activity and pulmonary lesions in adult subjects. Particularly, eventual changes and microscopic alterations in the thymus were studied and searched for in a KRAS-induced lung cancer murine model. MATERIAL AND METHODS An observational prospective study was conducted on a preclinical murine model in which KRAS induced lung cancer was expected and the thymic structure was analyzed. According to the stage of the neoplastic disease, the population of the study was divided in two groups: early stage, in case of singular lesions or few lesions defined as precocious phenocopies; advanced stage, in case of multiple neoplastic lesions. Four microscopic variables of the thymic structure were compared: presence/absence of the medullary portion; cortex/medullary ratio; perithymic tissue (normal adipose vs normal adipose + brown-like adipose tissue); presence/absence of thymic involution. Statistical analyses were made to compare the two groups. RESULTS The population of the study was composed by 19 mice. Excluding one negative control and one without neoplastic lesions, the 17 mice were divided in: 6 in the early stage group and 11 in the advanced one. No differences between the two groups were found according the 4 microscopic variables. The thymic involution and the absence of the medullary portion, together with a non-distinguishable C:M ratio, were all detected only in the advanced group. Furthermore, the perithymic brown-like adipose tissue was markedly more present in this group rather than in the early one. DISCUSSION In the end, a link would be found between the state of the thymus and the disease, more specifically between the thymic involution state, well-ordered and distinguishable architecture with the severity of the disease. More studies with more significant numbers and more elaborated timelines are definitely needed, in the prospective of deepening our knowledge of the thymic function in the context of solid pulmonary and extra-pulmonary neoplastic diseases.