Functional Engagement of the PD-1/PD-L1 Complex But Not PD-L1 Expression Is Highly Predictive of Patient Response to Immunotherapy in Non-Small-Cell Lung Cancer.

PURPOSE: In many cancers, the expression of immunomodulatory ligands leads to immunoevasion, as exemplified by the interaction of PD-L1 with PD-1 on tumor-infiltrating lymphocytes. Profound advances in cancer treatments have come with the advent of immunotherapies directed at blocking these immuno-suppressive ligand-receptor interactions. However, although there has been success in the use of these immune checkpoint interventions, correct patient stratification for these therapies has been challenging. MATERIALS AND METHODS: To address this issue of patient stratification, we have quantified the intercellular PD-1/PD-L1 interaction in formalin-fixed paraffin-embedded tumor samples from patients with non-small cell lung carcinoma, using a high-throughput automated quantitative imaging platform (quantitative functional proteomics [QF-Pro]). RESULTS: The multisite blinded analysis across a cohort of 188 immune checkpoint inhibitor-treated patients demonstrated the intra- and intertumoral heterogeneity of PD-1/PD-L1 immune checkpoint engagement and notably showed no correlation between the extent of PD-1/PD-L1 interaction and PD-L1 expression. Importantly, PD-L1 expression scores used clinically to stratify patients correlated poorly with overall survival; by contrast, patients showing a high PD-1/PD-L1 interaction had significantly better responses to anti-PD-1/PD-L1 treatments, as evidenced by increased overall survival. This relationship was particularly strong in the setting of first-line treatments. CONCLUSION: The functional readout of PD-1/PD-L1 interaction as a predictive biomarker for the stratification of patients with non-small-cell lung carcinoma, combined with PD-L1 expression, should significantly improve the response rates to immunotherapy. This would both capture patients excluded from checkpoint immunotherapy (high PD-1/PD-L1 interaction but low PD-L1 expression, 24% of patients) and additionally avoid treating patients who despite their high PD-L1 expression do not respond and suffer from side effects.

Pure white cell aplasia an exceptional condition in the immunological conundrum of thymomas: Responses to immunosuppression and literature review.

Thymomas are tumours frequently associated with autoimmune manifestations or immunodeficiencies like Good syndrome. In rare cases, pure white cells aplasia (PWCA) has been described in association with thymomas. PWCA is characterized by agranulocytosis of autoimmune background primary refractory to granulocyte colony-stimulating factor (G-CSF). It is necessary the use of immunosuppressor to allow granulocyte recovery. Without treatment, it could be fatal.

[Paratesticular fibrous pseudotumor]. / Pseudotumor fibroso paratesticular.

OBJECTIVE: Benign testicular proliferative processes are known by the name of pseudotumors, because currently they are not considered real neoplasias. The paratesticular fibrous pseudotumor (PFP) is a rare entity the definition and etiopathogenesis of which is under great confusion. It is a process that misleads the clinical because they simulate neoplasias. This paper aims to help a better knowledge of this non-tumoral process and to avoid diagnostic confusions. METHODS/RESULTS: We review our series of PFP (three cases), which can be considered significant due to its oddity. We analyze the clinical picture, its behavior, imaging diagnostic tests, operative findings and outcomes. CONCLUSIONS: PFP is a rare entity which may misleads the clinical because it may be diagnosed as a neoplasia and lead to aggressive treatment (orchiectomy) which in case of a proper diagnosis could be avoided. The analysis of our series of three cases, with their contribution, and a literature review may help the clinical practice of urologists by recognizing this disease.