Myasthenia gravis is present in a significant proportion of patients with thymoma. We investigated particular features of the clinical behavior of thymoma and its relationship to myasthenia in a retrospective study of 79 patients who underwent thymectomy for thymoma during the last 20 years. The presence of myasthenia gravis, Masaoka stage, World Health Organization histotype, myasthenia response, and survival were analyzed. The mean age of the patients was 56.1 ±12.4 years, and 39 had myasthenia gravis. A significantly higher proportion of patients with myasthenia was found in B2 and B3 histotypes compared to A, AB, and B1. Among myasthenic patients, 33.3% had no response, 50% had a partial response, and 16.7% achieved complete remission. During the follow-up period, 16 (21.1%) patients died. Mean survival was 4.8 ± 1.4 years for patients with no myasthenia response, whereas those with a partial or complete myasthenia response had significantly better survival.

A key unknown of the functional space in tumor immunity is whether physiologically relevant cancer antigen presentation occurs solely in draining lymph nodes versus tumors. Professional antigen presenting cells, i.e. the dendritic cells, are scarce and immature within tumors, greatly outnumbered by MHCII expressing non-hematopoietic cells, such as antigen-presenting cancer-associated fibroblasts (apCAFs). We hypothesized that after their exit from tumor-draining lymph nodes T cells depend on a second wave of antigen presentation provided in situ by structural cells. We show that dense apCAF regions in human lung tumors define hot immunological spots with increased numbers of CD4 T cells. The transcriptomic profile of human lung apCAFs aligned to that of pancreatic apCAFs across mice and humans and were both enriched for alveolar type II genes, suggesting an epithelial origin. Mechanistically, human apCAFs directly activated the TCRs of adjacent effector CD4 T cells and at the same time produced high levels of c1q, which acted on surface c1qbp on T cells to rescue them from apoptosis. Fibroblast-specific deletion of MHCII in mice impaired local MHCII immunity and accelerated tumor growth, while inducing c1qbp overexpression in adoptively transferred T cells expanded their numbers within tumors and reduced tumour burden. Collectively, our work shows that tumor T cell immunity post lymph node exit requires peripheral antigen presentation by a subset of CAFs and proposes a new conceptual framework upon which effective cancer immunotherapies can be built.

Background/Objectives: Total cell-free DNA (cfDNA) is not tumour-specific and may be affected by peri-operative injury and inflammation. We evaluated peri-operative plasma cfDNA dynamics and explored associations with recurrence and mortality in resectable non-small cell lung cancer (NSCLC). Methods: This prospective pilot cohort included 35 patients undergoing lobectomy with systematic nodal dissection and 30 healthy controls. Samples were collected pre-operatively, from the tumour-draining pulmonary vein before major manipulation, peripherally after resection, and on postoperative day 14. Analyses included group comparisons, receiver operating characteristic analysis, logistic regression and Cox regression. Results: Pre-operative cfDNA was higher in patients than controls (mean 1.96 versus 1.08 ng/µL; p = 0.002). Discrimination was modest (AUC 0.67, 95% CI 0.54–0.80), with sensitivity 49% and specificity 93% at an internally selected cut-off. cfDNA differed across timepoints (overall p = 0.008), with higher intra-operative and post-resection values than pre-operative values. Among 34 patients with complete three-year outcomes, 12 recurred and 13 died. Pre-operative cfDNA was associated with recurrence in multivariable logistic regression (adjusted OR 2.47, 95% CI 1.07–5.67; p = 0.034). Day-14 cfDNA was higher among patients who died (5.35 versus 2.17 ng/µL; p = 0.008). Conclusions: Total cfDNA showed modest diagnostic discrimination and exploratory outcome associations. Small sample size, potential model overfitting and incomplete analytical documentation limit interpretation. These hypothesis-generating findings require independent validation with standardised methods, peri-operative covariates and tumour-informed circulating tumour DNA assays.