Pathologic complete response to preoperative immunotherapy in a lung adenocarcinoma patient with bone metastasis: A case report

AbstractAnti ‐programmed cell death 1 (PD‐1) and its ligand (PD‐L1) has emerged as a novel immunotherapy for non‐small cell lung cancer (NSCLC). However, the proportion of patients who may benefit from immunotherapy is limited and the factors sensitive or resistant to immunotherapy are not completely cle ar. Therefore, to identify reliable biomarkers as predictors of clinical response and resistance to anti‐PD‐1/PD‐L1 therapies have become increasingly important. Here, we report a case of a patient with bone metastatic NSCLC, who achieved a pathologic complete response after preoperative pembr olizumab treatment. Postoperative pathological examination found no viable cancer cells in the resected pulmonary nodules and lymph nodes. Several high‐frequency DNA damage response and repair (DDR) gene mutations including two germline mutations were identified in the primary lesion. Moreover, hi gh PD‐L1 expression, Kirsten rat sarcoma viral oncogene homolog (KRAS) combined with tumor protein 53 (TP53) mutations without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) driver alterations, high infiltration level of CD8 ‐positive cells and M1 macrophages were observed, which were favorable characteristics for immunotherapy. We explored the possible factors related to an excellent response to immune checkpoint inhibitor in this patient and determined that preoperative use of anti‐PD‐1 therapy might apply to la te‐stage lung adenocarcinoma...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: CASE REPORT Source Type: research

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Conclusions and Future Perspectives It is now evident that NK/ILC family plays a pivotal role in the immune defenses. Recent studies in murine and human settings demonstrated that the expression of several inhibitory checkpoints, that may be detrimental in the tumor context, is not restricted to T lymphocytes, revealing an important, yet poorly appreciated, contribution of their expression on innate immune cells. Thus, in the recent years different immunotherapy approaches, based on the blockade of inhibitory NK cell receptors, have been developed in order to unleash NK cell cytotoxicity. This is particularly important in...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, several biopsies from a patient-derived primary renal-cell carcinoma were analyzed by whole-exome sequencing and aligned to healthy tissue. Next to several shared mutations between different subclones, ca. 23% of the mutations were only found in specific regions of the tumor. Strikingly, a single biopsy of that same tumor only covered around 55% of the total mutational diversity, underlining the need for multi-region sampling. Tracing the order of mutations in different subclones revealed that they develop in a branching fashion from the primary tumor clone, harboring the driver mutation, rather than in a li...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions In the new era of targeted therapy, treatment options are increasingly based on the precise molecular and genetic profiling of tumor cells (58). Currently, the main challenge for further novel drug development in targeted therapy is the clarification of specific molecular mechanisms underlying the varied forms of tumors in clinic. It has been acknowledged that cancer is caused by a set of driver mutations. In this regard, it is of great significance to: (1) identify and validate key mutant genes and proteins in cancers as new targets; (2) identify patients most likely and unlikely to benefit from certain targe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: EBUS-TBNA with a 21-gauge needle is appropriate for the analysis of multiple mutations and the genotyping of lung adenocarcinoma. PMID: 30075474 [PubMed - in process]
Source: Southern Medical Journal - Category: General Medicine Tags: South Med J Source Type: research
We report our experience of ALK testing with immunohistochemistry (IHC) and fluorescence in-situ hybridisation (FISH) and present the prevalence of EGFR, Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) and ALK mutations. From January 2011 to May 2014, we found mutation rates of EGFR, KRAS and ALK to be 10.4% (67/643), 35.8% (86/240) and 2.3% (7/304), respectively. ALK-rearrangements were found to be associated with never smokers (p
Source: Journal of the Royal College of Physicians of Edinburgh - Category: General Medicine Tags: J R Coll Physicians Edinb Source Type: research
Background and objective Anaplastic lymphoma kinase (ALK) is one of the major driver genes of non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy of pemetrexed in ALK-positive lung cancer is controversial. The aim of this study is to explore the efficacy of pemetrexed-based chemotherapy in patients with ALK-positive and negative lung adenocarcinoma. Methods The clinical data of 98 cases of epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene (KRAS), V-rafmurine sarcoma viral oncogene homolog B1 (BRAF)-negative patients with advanced lung adenocarcinoma patients who diagno...
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology Source Type: research
Opinion statementPersonalized targeted therapy has emerged as a promising strategy in lung cancer treatment, with current attention focused on elucidation and detection of oncogenic drivers responsible for tumor initiation and maintenance and development of drug resistance. In lung cancer, several oncogenic drivers have been reported, triggering the application of tyrosine kinase inhibitors (TKIs) to target these dysfunctional genes. The anaplastic lymphoma kinase (ALK) rearrangement is responsible for about 4 –7% of all non-small cell lung cancers (NSCLCs) and perhaps as high as a third in specific patient populatio...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Cho J, Choi SM, Lee J, Lee CH, Lee SM, Kim DW, Yim JJ, Kim YT, Yoo CG, Kim YW, Han SK, Park YS Abstract BACKGROUND: The proportion of never-smokers with non-small cell lung cancer (NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never-smokers with NSCLC in a large single institution. METHODS: We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014. RESULTS: Of the 1860 NSCLC patients, 707 (38.0%) were never-smokers. The propor...
Source: Chinese Journal of Cancer - Category: Cancer & Oncology Tags: Chin J Cancer Source Type: research
Background and objective Molecular targeted therapy has gradually become an important treatment for lung cancer, the aim of this research is to analyze the clinicopathologic features associated with the gene mutation status of epidermal growth factor receptor (EGFR), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and Kirsten rat sarcoma viral oncogene (KRAS) in non-small cell lung cancer (NSCLC) patients and determine the most likely populations to benefit from molecular target therapy treatment. Methods The mutation status of EG...
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology Source Type: research
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