Next Article in Journal
BRCA Methylation Testing Identifies a Subset of Ovarian Carcinomas without Germline Variants That Can Benefit from PARP Inhibitor
Next Article in Special Issue
The Next-Generation Immune Checkpoint LAG-3 and Its Therapeutic Potential in Oncology: Third Time’s a Charm
Previous Article in Journal
N-Docosahexanoylethanolamine Reduces Microglial Activation and Improves Hippocampal Plasticity in a Murine Model of Neuroinflammation
Previous Article in Special Issue
Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?
Communication

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

1
Department of Respiratory Medicine, Kumamoto Chuo Hospital, Kumamoto-shi, Kumamoto 860-8556, Japan
2
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto-shi, Kumamoto 860-8556, Japan
3
Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20814, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(24), 9705; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249705
Received: 28 November 2020 / Revised: 14 December 2020 / Accepted: 16 December 2020 / Published: 19 December 2020
Evolution of tumor-immune microenviroments (TIMEs) occurs during tumor growth and dissemination. Understanding inter-site tumor-immune heterogeneity is essential to harness the immune system for cancer therapy. While the development of immunotherapy against lung cancer with driver mutations and neuroendocrine tumors is ongoing, little is known about the TIME of large cell neuroendocrine carcinoma (LCNEC) or anaplastic lymphoma kinase (ALK) rearrangement-positive lung cancer. 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. View Full-Text
Keywords: anaplastic lymphoma kinase (ALK); B cell; heterogeneity; immune checkpoint; large cell neuroendocrine carcinoma (LCNEC); neuroendocrine tumors (NET); regulatory T-cells (Tregs); programmed death-ligand 1 (PD-L1); tumor-infiltrating lymphocyte (TIL); tumor-immune microenvironments (TIME) anaplastic lymphoma kinase (ALK); B cell; heterogeneity; immune checkpoint; large cell neuroendocrine carcinoma (LCNEC); neuroendocrine tumors (NET); regulatory T-cells (Tregs); programmed death-ligand 1 (PD-L1); tumor-infiltrating lymphocyte (TIL); tumor-immune microenvironments (TIME)
Show Figures

Graphical abstract

MDPI and ACS Style

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. Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma. Int. J. Mol. Sci. 2020, 21, 9705. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249705

AMA Style

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. Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma. International Journal of Molecular Sciences. 2020; 21(24):9705. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249705

Chicago/Turabian Style

Tashiro, Takahiro, Kosuke Imamura, Yusuke Tomita, Daisuke Tamanoi, Akira Takaki, Kazuaki Sugahara, Ryo Sato, Koichi Saruwatari, Shinya Sakata, Megumi Inaba, Sunao Ushijima, Naomi Hirata, and Takuro Sakagami. 2020. "Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma" International Journal of Molecular Sciences 21, no. 24: 9705. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249705

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop