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1.
Lancet Oncol ; 21(10): e463-e476, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002442

RESUMO

Immunotherapy represents a paradigm shift in oncology treatment. The goal of immunotherapy is to overcome immunosuppression induced by a tumour and its microenvironment, thereby allowing the immune system to target and kill cancer cells. The immunotherapy era began when the first immune checkpoint inhibitor, ipilimumab, was approved for use almost a decade ago. This therapeutic approach is associated with distinct types of response, including processes such as pseudoprogression (ie, increased tumour burden via radiology, which is not accompanied by clinical deterioration) and hyperprogression (ie, rapid progression of the disease as a result of immunotherapy). In this Review, we focus on therapeutic approaches for patients who progress on immunotherapy. We review the different types of clinical responses associated with immunotherapy and describe treatment options for this population.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Imunoterapia/efeitos adversos , Neoplasias/terapia , Algoritmos , Antineoplásicos Imunológicos/efeitos adversos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Humanos , Critérios de Avaliação de Resposta em Tumores Sólidos , Terapia de Salvação
2.
Nat Commun ; 11(1): 4946, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009409

RESUMO

Immune-related adverse events (irAEs), caused by anti-PD-1/PD-L1 antibodies, can lead to fulminant and even fatal consequences and thus require early detection and aggressive management. However, a comprehensive approach to identify biomarkers of irAE is lacking. Here, we utilize a strategy that combines pharmacovigilance data and omics data, and evaluate associations between multi-omics factors and irAE reporting odds ratio across different cancer types. We identify a bivariate regression model of LCP1 and ADPGK that can accurately predict irAE. We further validate LCP1 and ADPGK as biomarkers in an independent patient-level cohort. Our approach provides a method for identifying potential biomarkers of irAE in cancer immunotherapy using both pharmacovigilance data and multi-omics data.


Assuntos
Genômica , Imunoterapia/efeitos adversos , Neoplasias/imunologia , Neoplasias/terapia , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Análise Fatorial , Humanos , Proteínas dos Microfilamentos/metabolismo , Reprodutibilidade dos Testes
3.
Lancet Oncol ; 21(9): e419-e430, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888471

RESUMO

Notable advances have been achieved in the treatment of cancer since the advent of immunotherapy, and immune checkpoint inhibitors have shown clinical benefit across a wide variety of tumour types. Nevertheless, most patients still progress on these treatments, highlighting the importance of unravelling the underlying mechanisms of primary resistance to immunotherapy. A well described biomarker of non-responsiveness to immune checkpoint inhibitors is the absence or low presence of lymphocytes in the tumour microenvironment, so-called cold tumours. There are five mechanisms of action that have the potential to turn cold tumours into so-called hot and inflamed tumours, hence increasing the tumour's responsiveness to immunotherapy-increasing local inflammation, neutralising immunosuppression at the tumour site, modifying the tumour vasculature, targeting the tumour cells themselves, or increasing the frequency of tumour-specific T cells. In this Review, we discuss preclinical data that serves as the basis for ongoing immunotherapy clinical trials for the treatment of non-immunoreactive tumours, as well as reviewing clinical and translational data where available. We explain how improving our understanding of the underlying mechanisms of primary resistance to immunotherapy will help elucidate an increasingly granular view of the tumour microenvironment cellular composition, functional status, and cellular localisation, with the goal of further therapy refinement.


Assuntos
Resistencia a Medicamentos Antineoplásicos/imunologia , Imunoterapia/efeitos adversos , Inflamação/terapia , Neoplasias/terapia , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Quinase 1 do Ponto de Checagem/imunologia , Ensaios Clínicos como Assunto , Humanos , Imunidade Celular/imunologia , Inflamação/imunologia , Inflamação/patologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Microambiente Tumoral/imunologia
4.
Anticancer Res ; 40(9): 4875-4883, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878775

RESUMO

BACKGROUND/AIM: Some reports showed encouraging efficacy of immune checkpoint inhibitors among patients who experienced immune-related adverse events (irAEs). Thus, characterization of T-cell repertoire and immune signatures in peripheral blood mononuclear cells (PBMCs) and tumors before and after immune checkpoint inhibitors treatment should contribute to better understanding of irAE-provoked anticancer immune responses. MATERIALS AND METHODS: We applied expression analysis of immune-related genes and T-cell receptor sequencing in tumor and PBMCs from five patients with renal cell carcinoma before combined immunotherapy and at the onset of severe irAEs. RESULTS: We found that the cluster of differentiation 8 (CD8)/forkhead box P3(FOXP3), granzyme B(GZMB)/CD3, perforin 1(PRF1)/CD3 and programmed cell death 1(PD1)/CD8 expression ratios were significantly elevated in PBMCs at the onset of irAEs. In addition, we found expansion of certain T-cell clones in metastatic tissue after irAEs, which were already increased in peripheral blood at the onset of irAEs. CONCLUSION: irAE-provoked T-cells may also circulate and attack distant tumors, leading to durable response in patients with irAEs.


Assuntos
Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/terapia , Imunoterapia/efeitos adversos , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Feminino , Perfilação da Expressão Gênica , Genes Codificadores dos Receptores de Linfócitos T/genética , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia
5.
Anticancer Res ; 40(10): 5445-5456, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988866

RESUMO

BACKGROUND/AIM: Dietary interventions like time-restricted feeding (TRF) show promising anti-cancer properties. We examined whether therapeutic TRF alone or combined with immunotherapy would diminish renal tumor growth in mice of varying body weights. MATERIALS AND METHODS: Young (7 week) chow-fed or older (27 week) high-fat diet (HFD)-fed BALB/c mice were orthotopically injected with renal tumor cells expressing luciferase. After tumor establishment, mice were randomized to ad libitum feeding or TRF +/- anti-CTLA-4. Body composition, tumor viability and growth, and immune responses were quantified. RESULTS: TRF alone reduced renal tumor bioluminescence in older HFD-fed, but not young chow-fed mice. In the latter, TRF mitigated tumor-induced loss of lean- and fat-mass. However, TRF did not alter excised renal tumor weights or intratumoral immune responses and failed to improve anti-CTLA-4 outcomes in any mice. CONCLUSION: Therapeutic TRF exhibits modest anti-cancer properties but fails to improve anti-CTLA-4 immune checkpoint blockade in murine renal cancer.


Assuntos
Jejum , Neoplasias Renais/tratamento farmacológico , Obesidade/tratamento farmacológico , Animais , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Modelos Animais de Doenças , Ingestão de Alimentos/fisiologia , Humanos , Imunoterapia/efeitos adversos , Neoplasias Renais/complicações , Neoplasias Renais/genética , Neoplasias Renais/patologia , Camundongos , Obesidade/complicações , Obesidade/genética
6.
Immunotherapy ; 12(15): 1133-1138, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32900245

RESUMO

Background: Little is known about the 2019 novel coronavirus disease (COVID-19) course and outcomes in patients receiving immunotherapy. Here we describe a metastatic Merkel cell carcinoma patient with a severe acute respiratory syndrome coronavirus 2 infection while receiving pembrolizumab. Case presentation: A 66-year-old man, with a metastatic Merkel cell carcinoma receiving pembrolizumab, presented with fever. Chest computed tomography (CT) showed pulmonary ground-glass opacities, suggesting viral or immuno-related etiology. On day 7, the patient was hospitalized due to dyspnea and worsening of the radiological findings. Real time polymerase chain reaction (RT-PCR) testing confirmed COVID-19. The patient developed acute respiratory distress syndrome and acute kidney injury. Hydroxychloroquine was administered for 5 days, but discontinued after supraventricular extrasystoles. Clinical improvement allowed the patient's discharge after 81 days of hospitalization. Conclusion: A careful evaluation of oncologic patients receiving immunotherapy during the COVID-19 pandemic is of utmost importance.


Assuntos
Carcinoma de Célula de Merkel/terapia , Infecções por Coronavirus/diagnóstico , Imunoterapia , Pneumonia Viral/diagnóstico , Neoplasias Cutâneas/terapia , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Betacoronavirus , Carcinoma de Célula de Merkel/complicações , Carcinoma de Célula de Merkel/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Humanos , Imunoterapia/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
PLoS One ; 15(7): e0236374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735564

RESUMO

We recently reported the development of a fully-human, CD3-binding bispecific antibody for immunotherapy of malignant glioma. To translate this therapeutic (hEGFRvIII-CD3- bi-scFv) to clinical trials and to help further the translation of other similar CD3-binding therapeutics, some of which are associated with neurologic toxicities, we performed a good laboratory practice (GLP) toxicity study to assess for potential behavioral, chemical, hematologic, and pathologic toxicities including evaluation for experimental autoimmune encephalomyelitis (EAE). To perform this study, male and female C57/BL6 mice heterozygous for the human CD3 transgene (20/sex) were allocated to one of four designated groups. All animals were administered one dose level of hEGFRvIII-CD3 bi-scFv or vehicle control. Test groups were monitored for feed consumption, changes in body weight, and behavioral disturbances including signs of EAE. Urinalysis, hematologic, and clinical chemistry analysis were also performed. Vehicle and test chemical-treated groups were humanely euthanized 48 hours or 14 days following dose administration. Complete gross necropsy of all tissues was performed, and selected tissues plus all observed gross lesions were collected and evaluated for microscopic changes. This included hematoxylin-eosin histopathological evaluation and Fe-ECR staining for myelin sheath enumeration. There were no abnormal clinical observations or signs of EAE noted during the study. There were no statistical changes in food consumption, body weight gain, or final body weight among groups exposed to hEGFRvIII-CD3 bi-scFv compared to the control groups for the 2- and 14-day timepoints. There were statistical differences in some clinical chemistry, hematologic and urinalysis endpoints, primarily in the females at the 14-day timepoint (hematocrit, calcium, phosphorous, and total protein). No pathological findings related to hEGFRvIII-CD3 bi-scFv administration were observed. A number of gross and microscopic observations were noted but all were considered to be incidental background findings. The results of this study allow for further translation of this and other important CD3 modulating bispecific antibodies.


Assuntos
Anticorpos Biespecíficos/farmacologia , Complexo CD3/imunologia , Receptores ErbB/imunologia , Glioma/imunologia , Animais , Anticorpos Biespecíficos/imunologia , Peso Corporal/efeitos dos fármacos , Peso Corporal/imunologia , Complexo CD3/farmacologia , Modelos Animais de Doenças , Receptores ErbB/farmacologia , Feminino , Glioma/patologia , Glioma/terapia , Humanos , Imunoterapia/efeitos adversos , Masculino , Camundongos , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
8.
Orv Hetil ; 161(28): 1151-1165, 2020 07.
Artigo em Húngaro | MEDLINE | ID: mdl-32609623

RESUMO

Oncorheumatology is the meeting point of tumour formation and rheumatic diseases. Multiple interactions exist between these two medical specialties. One major field is the topic of malignancies associated with rheumatic diseases, while the other topic covers the development of musculoskeletal disease in cancer patients. In the first group, secondary malignancies associated with rheumatic diseases, role of tumour-associated antigens in rheumatology, the possible carcinogenicity of conventional and targeted antirheumatic drugs and physical therapy of rheumatic patients with recent or current cancer will be discussed. The second large topic includes paraneoplastic syndromes, autoimmune-rheumatic side effects of oncotherapies (chemotherapy and immunotherapy), effects of hormone-deprivation therapies on bone and primary and secondary malignancies of the musculoskeletal system. Orv Hetil. 2020; 161(28): 1151-1165.


Assuntos
Antineoplásicos/efeitos adversos , Doenças Musculoesqueléticas/patologia , Neoplasias/imunologia , Neoplasias/patologia , Síndromes Paraneoplásicas/imunologia , Doenças Reumáticas/imunologia , Doenças Reumáticas/patologia , Humanos , Imunoterapia/efeitos adversos , Síndromes Paraneoplásicas/patologia
11.
Z Rheumatol ; 79(6): 545-553, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32613268

RESUMO

Immune checkpoint inhibitors (ICPi) represent a major breakthrough in the treatment and prognosis of many cancers, particularly of malignant melanoma and non-small cell lung cancer; however, the high tumor response rates with ICPi are also frequently associated with autoimmune side effects, so-called immune-related adverse events (irAEs), which can involve virtually any organ system and mirror classical autoimmune diseases. Recent studies revealed that around 5-20% of patients treated with ICPi experience rheumatic irAEs covering the full spectrum of inflammatory rheumatic diseases. This article summarizes the state of the art of knowledge with respect to diagnostics and management of this newly recognized disease entity in rheumatology.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Doenças Reumáticas , Reumatologia , Autoimunidade , Carcinoma Pulmonar de Células não Pequenas , Humanos , Fatores Imunológicos , Neoplasias Pulmonares , Doenças Reumáticas/induzido quimicamente , Doenças Reumáticas/imunologia
14.
Rev Med Suisse ; 16(696): 1165-1168, 2020 Jun 03.
Artigo em Francês | MEDLINE | ID: mdl-32496706

RESUMO

Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, by reshaping the prognosis of many cancers and are progressively becoming the standard of care. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), of which cardiovascular irAEs are particularly feared. ICI-induced myocarditis is often a diagnostic challenge because of the vast heterogeneity of clinical presentations, and it is associated with a high mortality rate of around 50%. The present article summarizes the cardiac manifestations, the diagnostic strategy and the therapeutic management of patients with ICI-induced myocarditis used in the treatment of cancer.


Assuntos
Cardiotoxicidade/etiologia , Imunoterapia/efeitos adversos , Miocardite/induzido quimicamente , Neoplasias/tratamento farmacológico , Humanos , Neoplasias/imunologia , Neoplasias/patologia
15.
Autoimmun Rev ; 19(8): 102595, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32535092

RESUMO

OBJECTIVE: Although immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, their use is associated with immune toxicities referred to as immune-related adverse events (irAE). Here we describe the clinical presentation and management of rheumatic immune-related adverse events (Rh-irAE) in a national multi-center cohort. METHODS: All patients presenting with Rh-irAE at 9 academic sites across Canada between January 2013 and January 2019 were identified and included in this retrospective cohort study. Standardized data were extracted by chart review. RESULTS: 117 patients who developed 136 Rh-irAE were identified. The most frequent Rh-irAE was symmetric polyarthritis (n = 45). Other Rh-irAE included non-inflammatory musculoskeletal symptoms (n = 18), polymyalgia rheumatica (n = 17) and myositis (n = 9). Prednisone was the most commonly used treatment (n = 76) with a mean maximum dose of 60 ± 74 mg/d and duration of treatment of 8.4 ± 11 months. Forty-two patients required conventional synthetic disease-modifying anti-rheumatic drugs (DMARD) and two required biologic DMARD to control the Rh-irAE. ICI was discontinued due to the Rh-irAE in 22 patients. There were no deaths related to Rh-irAE. Treatment of the Rh-irAE did not appear to negatively impact the tumor response to immunotherapy with 23 patients experiencing tumor progression prior to treatment of the Rh-irAE and 13 following treatment. CONCLUSION: In this largest multi-center cohort of Rh-irAE described to date, symmetric polyarthritis was the most common Rh-irAE. There was considerable heterogeneity of treatment, although this did not appear to negatively impact the anti-tumor response. This study can inform the development of evidence-based recommendations to optimize Rh-irAE and cancer outcomes in patients treated with ICI.


Assuntos
Neoplasias , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Canadá , Estudos de Coortes , Humanos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Doenças Reumáticas/induzido quimicamente
16.
Autoimmun Rev ; 19(8): 102587, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32553612

RESUMO

Therapy for advanced melanoma has deeply changed in the last decade with the introduction of checkpoint and BRAF/MEK inhibitors. Granulomatous reactions have been reported related to these drugs. We performed a systematic review of all the cases described in the medical literature by the search (("Melanoma"[Mesh]) AND ("Sarcoidosis"[Mesh] OR "Granuloma"[Mesh])). Ninety-one patients under immunotherapy were included in the analyses. The time from the initiation of the immunotherapy until the onset of sarcoidosis or sarcoid-like reaction (SLR) was 7.1 months (SD 9). Peripheral lymph nodes as the mode of onset were seen more frequently in patients under CTLA-4 inhibitors (p = .016) whereas in patients under BRAF/MEK inhibitors used to be in the form of specific skin lesions (p = .006). Chest X-ray stage I-II was the rule in the CTLA-4 and PD-1 groups. On the contrary, stage 0 accounted for 80% of the patients in the BRAF/MEK group examined for pulmonary involvement. Specific skin involvement was the most common manifestation apart from pulmonary involvement. It was more frequent in patients under BRAF/MEK inhibitors and especially in the form of papules. Splenic involvement was found also more frequently in patients under CTLA-4 inhibitors. Specific treatment for sarcoidosis/SLR was prescribed in 50 patients (58.8%), without differences among groups. Almost all patients presented a good prognosis independently of the decision made regarding their previous immunotherapy. CONCLUSION: Physicians should bear in mind the possibility of sarcoidosis/SLR after the initiation of checkpoint or BRAF/MEK inhibitors in patients diagnosed with advanced melanoma, especially in the form of skin involvement and mediastinal and peripheral lymph nodes. It is important to achieve an accurate diagnosis to rule out the possibility of cancer involvement. What to do with these drugs is yet to be clarified. It seems reasonable to prioritize cancer treatment so it is not mandatory to stop these drugs.


Assuntos
Antineoplásicos , Imunoterapia , Melanoma , Sarcoidose , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Humanos , Imunoterapia/efeitos adversos , MAP Quinase Quinase 1/antagonistas & inibidores , Melanoma/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Sarcoidose/induzido quimicamente
18.
Crit Rev Oncol Hematol ; 151: 102979, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32480349

RESUMO

Treatment of oncologic patients has progressed greatly the last few years with the development of immune checkpoint inhibitors (ICPIs). These drugs are associated with the immune system and, thus, may cause side effects of immune origin, the so called immune related adverse events (irAEs). Immune related AEs may actually affect all organs and systems and frequently resemble clinical entities commonly encountered in clinical practice. As ICPIs have improved both quality of life and life expectancy, clinicians of various specialties may need to deal with irAEs in their everyday practice. Therefore, they should be able to recognize them timely and treat them accordingly. Herein, we review the pathophysiology, clinical manifestations and treatment of irAEs.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunoterapia/efeitos adversos , Doenças Metabólicas/induzido quimicamente , Neoplasias/tratamento farmacológico , Humanos , Qualidade de Vida
19.
Eur J Cancer ; 135: 47-50, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32534244

RESUMO

The novel coronavirus (CoV) pandemic is a serious threat for patients with cancer, who have an immunocompromised status and are considered at high risk of infections. Data on the novel CoV respiratory disease (coronavirus disease 2019 [COVID-19]) in patients with cancer are still limited. Unlike other common viruses, CoVs have not been shown to cause a more severe disease in immunocompromised subjects. Along with direct viral pathogenicity, in some individuals, CoV infection triggers an uncontrolled aberrant inflammatory response, leading to lung tissue damage. In patients with cancer treated with immunotherapy (e.g. immune checkpoint inhibitors), COVID-19 may therefore represent a serious threat. After a thorough review of the literature on CoV pathogenesis and cancer, we selected several shared features to define which patients can be considered at higher risk of COVID-19. We combined these clinical and laboratory variables, with the aim of developing a score to weight the risk of COVID-19 in patients with cancer.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Hospedeiro Imunocomprometido/imunologia , Imunoterapia/efeitos adversos , Neoplasias/imunologia , Pneumonia Viral/epidemiologia , Fatores Etários , Betacoronavirus/imunologia , Comorbidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Medição de Risco , Fatores de Risco , Fatores Sexuais
20.
Cancer Invest ; 38(6): 365-371, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32559143

RESUMO

Immunotherapy is standard first-line therapy for advanced non-small cell lung cancer (NSCLC) either alone or in combination with chemotherapy. Despite significant benefits, immune checkpoint inhibitors (ICI) can cause toxicities within any organ, termed immune related adverse events. Pneumonitis is a potentially life-threatening complication of ICIs. Currently, there are no established guidelines for use of ICIs in patients with underlying autoimmune or interstitial lung disease (ILD) and few studies have been published. We present a case of first-line ICI-chemotherapy in a patient with metastatic NSCLC and ILD who suffered treatment related lung toxicity and acute worsening ILD, which lead to his death.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia/efeitos adversos , Doenças Pulmonares Intersticiais/mortalidade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico por imagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Tomografia Computadorizada por Raios X
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