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We studied the interaction of PD-1+ lymphocytes with Ovary Carcinoma Cancer Cells (OCC) in several patients with pleural metastasis using immunocytochemical staining of pleural liquid. In addition to the intact separate T-cells, we discovered ubiquitous PD1+ -OCC aggregates in which the lymphocytes showed significant signs of cell defects and degradation in the environment of the otherwise intact OCC. Formation of such complexes and subsequent destruction of lymphocytes may be a pathway to provide the nutritional supply and support further growth of cancer cells in plank tonic state, in absence of vascularization and angiogenesis, relevant to both progression of lung metastases and some primary tumors such as small cell lung carcinoma. Introduction High aggression of the metastatic tumors, particularly ubiquitous in the lungs, remains one of the major problems in managing cancer progression and treatment. For example, the pleural metastatic expression of Ki-67 is high whereas p53 is lower than in primary tumors [1]. However, an establishment and growth of early metastatic formations are still poorly understood and not really amenable to prevention. For the most part the metastatic tumor proliferation is considered in context of interaction with the related stromal cells, vascularization and angiogenesis. Tumor Infiltrating Lymphocytes (TIL) are promising agents in cancer therapy as indicated by ongoing clinical trials involving autologous isolates causing tumor lysis [2]. Development of the PD-1+ sub-population of activated lymphocytes has been linked to cancer progression and various drug strategies emerged related to the so-called immune checkpoint inhibitors (e.g., Keytruda) blocking this receptor. In this report, driven by the interest in metastatic tumors and the role of T-cells, we looked into interactions of plank tonic cancer cells with circulating lymphocytes in pleural isolates of several patients with metastatic ovary carcinoma and discovered widespread PD-1+ -OCC aggregates that are terminally destructive for lymphocytes but not damaging to OCC. |
