RESUMO
The effect of radiotherapy during immunotherapy on immune-related adverse events (irAEs) is not fully understood. We herein report a 74-year-old woman diagnosed with lung adenocarcinoma with programmed death ligand 1 expression ≥50% and treated with pembrolizumab. She developed fatal immune thrombocytopenia associated with pembrolizumab immediately following radiotherapy. A flow cytometry analysis of peripheral blood detected an increased expression of programmed death-1 (PD-1) and Ki-67 in CD4+ and CD8+ T cells after radiotherapy, compared with pre-irradiation measurements. This case suggests that radiotherapy may evoke irAEs during treatment with anti-PD-1 antibodies, which physicians should consider when using radiotherapy in patients treated with these drugs.
Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos Imunológicos , Neoplasias Pulmonares , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/radioterapia , Idoso , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/efeitos adversos , Linfócitos T CD8-Positivos , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológicoRESUMO
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.
Assuntos
Quinase do Linfoma Anaplásico/genética , Carcinoma Neuroendócrino/patologia , Rearranjo Gênico , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral , Microambiente Tumoral , Adulto , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Radiation recall dermatitis (RRD) is an inflammatory reaction that occurs at previously irradiated skin regions after drug administration. We herein report a patient with non-small-cell lung cancer treated previously with thoracic radiotherapy who developed severe RRD induced by atezolizumab [anti-programmed death 1 ligand 1 (PD-L1) antibody]. Immunohistochemistry of the skin biopsy showed dermatitis with infiltration of CD8+ lymphocytes, suggesting that atezolizumab might provoke an immune-related inflammatory reaction at previously irradiated skin regions. When administering anti-PD-L1 antibody to patients who have undergone radiotherapy previously, physicians should carefully monitor the irradiated skin for the potential occurrence of RRD.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Radiodermite/diagnóstico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Terapia Combinada/efeitos adversos , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Radiodermite/induzido quimicamente , Radiodermite/patologia , Índice de Gravidade de DoençaRESUMO
PD-1 blockade therapy activates T cells by blocking the interaction between PD-1 and PD-L1 and promotes IFN-γ and Th1 cytokine production. In turn, IFN-γ and Th1 cytokines produced by activated T cells promote TF synthesis in monocytes/macrophages, which results in hypercoagulability leading to thrombosis.