Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma

We present a case study of a 32-year-old female patient with ALK-rearrangement-positive LCNEC, who had multiple distant metastases including mediastinal lymph-node, bilateral breasts, multiple bones, liver and brain. Multiple biopsy samples obtained from primary lung and three metastatic tumors were analyzed by fluorescent multiplex immunohistochemistry. Tissue localizations of tumor-infiltrating lymphocytes in the tumor nest and surrounding stroma were evaluated. T cell and B cell infiltrations were decreased with distance from primary lung lesion. Although each tumor displayed a unique TIME, all tumors exhibited concomitant regression after treatment with an ALK-inhibitor. This study provides the first evidence of the coexistence of distinct TIME within a single individual with ALK-rearrangement-positive LCNEC. The present study contributes to our understanding of heterogeneous TIMEs between primary and metastatic lesions and provides new insights into the complex interplay between host-immunity and cancer cells in primary and metastatic lesions. READ ARTICLE

International Journal of Molecular Science DOI: 10.3390/ijms21249705

Authors: Tashiro T, Imamura K, Tomita Y, Tamanoi D, Takaki A, Sugahara K, Sato R, Saruwatari K, Sakata S, Inaba M, Ushijima S, Hirata N, Sakagami T

Case StudyKirk SmithDecember 19, 2020B cell, ALK, heterogeneity, immune checkpoint, large cell neuroendocrine carcinoma, LCNEC, neuroendocrine tumors, NET, PD-L1, regulatory T-cells, Tregs, tumor-immune microenvironments, TIME, tumor-infiltrating lymphocyte, TIL