Background: The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within the tumor microenvironment (TME). Unveiling the immune landscape of ESCC in the context of NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. Methods: We analyzed single cells from 22 baseline and 24 post-NAT treatment samples of stage II/III ESCC patients to explore the association between the immune landscape and pathological response to neoadjuvant anti-PD-1 combination therapy, including pathological complete response (pCR), major pathological response (MPR), and incomplete pathological response (IPR). Results: Single-cell profiling identified 14 major cell subsets of cancer, immune, and stromal cells. Trajectory analysis unveiled an interesting link between cancer cell differentiation and pathological response to NAT. ESCC tumors enriched with less differentiated cancer cells exhibited a potentially favorable pathological response to NAT, while tumors enriched with clusters of more differentiated cancer cells may resist treatment. Deconvolution of transcriptomes in pre-treatment tumors identified gene signatures in response to NAT contributed by specific immune cell populations. Upregulated genes associated with better pathological responses in CD8 + effector T cells primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, and negative regulation of the T cell apoptotic process, whereas downregulated genes were dominated by those in the immune response-activating cell surface receptor signaling pathway. Natural killer cells in pre-treatment tumors from pCR patients showed a similar upregulation of gene expression in response to IFNγ but a downregulation of genes in the neutrophil-mediated immunity pathways. A decreased cellular contexture of regulatory T cells in ESCC TME indicated a potentially favorable pathological response to NAT. Cell–cell communication analysis revealed extensive interactions between CCL5 and its receptor CCR5 in various immune cells of baseline pCR tumors. Immune checkpoint interaction pairs, including CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, and TNFSF4-TNFRSF4, might serve as additional therapeutic targets for ICI therapy in ESCC. Conclusions: This pioneering study unveiled an intriguing association between cancer cell differentiation and pathological response in esophageal cancer patients, revealing distinct subgroups of tumors for which neoadjuvant chemo-immunotherapy might be effective. We also delineated the immune landscape of ESCC tumors in the context of clinical response to NAT, which provides clinical insights for better understanding how patients respond to the treatment and further identifying novel therapeutic targets for ESCC patients in the future.

Background: Microwave ablation (MWA) has attracted a worldwide attention gradually in treating inoperable pulmonary malignancies. However, in the lung tissues treated with MWA recurrence of tumor may still occur and few data in large patient groups till now were reported about the safety or effectiveness of microwave ablation in treating primary lung cancer and metastatic pulmonary malignancies. The purpose of this study is to evaluate the clinical curative effect (local control, survival data) MWA and its safety as well. Methods: From 1 January 2005 to 1 January 2008, retrospective analyses, 69 patients underwent computed tomography (CT)-guided percutaneous MWA of pulmonary malignancies. All patients were deemed medically inoperable. The correlation of tumor sizes and local progression after ablation was analyzed and the survival rates within 3 years post surgery were compared between non-small-cell lung cancer and pulmonary metastases groups also. Results: Pneumothorax was the most frequent complication and occurred in 24.64% patients after ablation. Neither needle track implantation was found nor did patient death occur in these patients within 30 days. The 1-, 2-, and 3-year overall survival rates were 66.7%, 44.9% and 24.6%, respectively. The overall survival rates for NSCLC patients in 1 year, 2 years, and 3 years were 75.0%, 54.2%, and 29.2%, respectively. The overall survival rates for pulmonary metastatic tumor patients in 1 year, 2 years, and 3 years were 47.6%, 23.8%, and 14.3%, respectively. The recurrence-free survival rates for NSCLC patients in 1 year, 2 years, and 3 years were 72.9%, 50.0%, and 27.1%, respectively. The mortality rates for pulmonary metastatic tumor patients in 1 year, 2 years, and 3 years were 47.6%, 19.0%, and 14.3%, respectively. Conclusions: Percutaneous microwave coagulation therapy was one safe and effective method and could be beneficial for the improvement of inoperable pulmonary malignancies treatment effect.

Objective: This article aims to investigate the expression of vacuolar-H + −ATPase (V-ATPase) in non-small cell lung cancer (NSCLC) and its variations with pathological type and grade. Furthermore, to evaluate the chemotherapy drug sensitivity of different cancer tissues as well as its correlation with V-ATPase expression in NSCLC. Methods: V-ATPase expression was examined in 92 NSCLC tissue samples using the immunohistochemical Envision method and immunofluorescence assay. The location of V-ATPase expression was observed by confocal laser scanning microscopy and the difference of its expression rate was evaluated. The sensitivity of cancer tissues to chemotherapy drug was examined using MTT assay and its correlation with the V-ATPase expression was tested in NSCLC by Spearman rank correlation analysis. Results: V-ATPase expression was mainly localized in the cell membrane and cytoplasm. The expression rate of V-ATPase was 71.43% in squamous cell lung cancer, significantly lower than that of the lung adenocarcinoma (83.72%, P = 0.000). In different pathological grades of squamous cell lung cancer, the expression rate of V-ATPase was 58.33% in grade II, significantly lower than that of the grade III (84.00%, P = 0.014). The expression rate of V-ATPase in grade II lung adenocarcinoma was 76.67%, significantly lower than that of the grade ΙΙΙ adenocarcinoma (100.0%, P = 0.012). Correlation analysis showed that the sensitivity of NSCLC tissues to cyclophosphamide, gemcitabine, doxorubicin, paclitaxel and cisplatin was significantly correlated with the V-ATPase expression rate (P < 0.05). Conclusions: V-ATPase was overexpressed in NSCLC. The expression of V-ATPase was related to the pathological type and grade of cancer and was likely associated with chemotherapy drug resistance in NSCLC. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7515811511020000

Background: ATP-binding cassette sub-family G member 2 (ABCG2) is a protein that in humans is encoded by the ABCG2 gene. ABCG2 participates in efflux of many chemotherapeutic agents. ABCG2 is often expressed in hematopoietic progenitor or stem cells. Vacuolar-H + −ATPase (V-ATPase) plays a key role in adjusting and maintaining intracellular pH and in regulating the drug tolerance of cells. The TNM Classification of Malignant Tumours (TNM) is a cancer staging system that describes the extent of cancer in a patient’s body. In this study, the expression of ABCG2 and V-ATPase in esophageal squamous cancer cells was detected. Methods: Immunohistochemistry staining and Immunofluorescence double staining were used to detect the expression of ABCG2 and V-ATPase in in 66 cases of esophageal squamous cancer cells. Associations and differences in expression of ABCG2 with that of V-ATPase were analyzed. Results: Positive staining patterns for both ABCG2 (66.67%) and V-ATPase (68.18%) were located mainly in the plasma membrane and cytoplasm. Marked differences in expression were also shown (P < 0.001) among 3 groups of pathological grades and TNM stages in these carcinomas. Marked differences were also found for ABCG2 expression between the two groups in the pathological grades and in the TNM staging groups (P < 0.01), but not between the αb and βgroups. V-ATPase expression was statistically significant between the 2 groups in the pathological grades and TNM stages (P < 0.05). This was not evident between α and β groups of pathological grades or between αb and βof the TNM stages. Marked differences in expression of ABCG2 and V-ATPase were found between metastatic and non-metastatic groups in the same carcinomas (P < 0.0001). There was also a clear correlation between the expression of ABCG2 and V-ATPase (P ≤ 0.001) in the various groups of pathological grades and TNM stages. Conclusions: Both ABCG2 and V-ATPase were over-expressed in esophageal squamous cancer cells. Their expression was associated with pathological grade, TNM stage and tumor metastasis in esophageal squamous cancer cells, suggesting interaction relationship between them. ABCG2 and V-ATPase expression may be strongly associated with drug resistance and tumor metastasis. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3823783918433897

Novel neoadjuvant immunotherapy combined with chemotherapy (neoICT) has improved outcomes for patients with esophageal squamous-cell carcinoma (ESCC), but challenges persist in low response rates and therapy resistance. Little is known about the intra-tumoral heterogeneity in the ESCC tumor microenvironment (TME) that underlies differential responses to neoadjuvant therapy. We applied single-cell RNA sequencing (scRNA-seq) profiling and multiplexed immunofluorescence staining to thoroughly decipher the TME in ESCC specimens from a neoadjuvant anti-PD1 combination therapy clinical trial. The cancer-associated fibroblasts (CAFs) population showed the significant alteration in abundance following neoadjuvant therapy. Specifically, IL6 + CCL2 + immunomodulatory CAFs and a novel CD248 + mechanoresponsive CAFs subset exhibited increasing infiltration. Mechanistically, CD248 + mechanoresponsive CAFs approached and lined the tumor nest to physically block the infiltration of CD8 + T cells and drug delivery, while IL6 + CCL2 + immunomodulatory CAFs induced therapeutic resistance with distinct IL-6 expression. Among patients treated with neoICT, we observed prominent CAF-T cell interactions. In particular, the NECTIN2-TIGIT ligand-receptor pair was enriched in treated samples, and TIGIT was identified as the major inhibitory checkpoint of T cells. Our findings demonstrate distinct alterations in TME constituent responses to neoadjuvant immunotherapy and identify functional phenotypes of CAFs associated with unfavorable therapeutic responses in patients. This provides potential targets to enhance responses to neoadjuvant therapy in ESCC.

Isolated Crohn’s disease of the esophagus is rare, and accurate diagnosis and treatment in its early course are difficult. Most cases are often found very late, when severe strictures or other complications have occurred. We report the case of a male 60-year-old patient with complaints of progressive dysphagia for more than two months and the sudden appearance of heartburn for seven consecutive days. Clinical examination revealed severe esophageal stricture with a suspected fistula and mediastinitis. The patient received a successful esophagectomy. The resected specimen and pathological results confirmed a deep linear ulcer, chronic and noncaseating granulomatous inflammation, as well as a circular stricture of the esophagus with fistula into the mediastinum due to isolated esophageal Crohn’s disease.