Tumor-infiltrating lymphocytes and tumor-associated macrophages as potential predictors of lymph node metastases in major salivary gland cancers.

Purpose: The purpose of this study is to define if tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) could represent potential predictors of lymph node metastases (LNM) in salivary gland cancers (SGC). Methods: A selected number of immunohistochemical markers related to TILs (CD3, CD4, CD68, and FOXP3) and TAMs (CD68 and CD163) were investigated on major salivary gland cancers. TIL and TAM densities were measured on digital images using the open-source QuPath both in the tumor interior (TI) and invasive margin (IM). Correlation with pathologic N classification and follow-up clinical data was investigated. Results: A total of 25 consecutive patients (men: 11; median age: 62.0) were included. Densities of CD3+ IM (OR = 7.7, 95% CI 1.2-51.2), CD8+ TI (OR = 7.7, 95% CI 1.2-51.2), CD8+ IM (OR = 7.7, 95% CI 1.2-51.2), FOXP3+ TI (OR = 24.0, 95% CI 2.2-255.9), CD68+ TI (OR = 7.7, 95% CI 1.2-51.2), and CD163+ IM (OR = 7.7, 95% CI 1.2 - 51.2), and the Immunoscore CD8/CD3 (OR = 1.9, 95% CI 1.1-3.4) were significantly associated with LNM (p < 0.05). CD3+ TI density was significantly associated with tumor recurrence and death (HR = 5.8, 95% CI 1.5-22.6; p < 0.05). Conclusion: A high density of specific TIL and TAM subpopulations might be correlated with a higher probability of LNM in SGC.

Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. METHODS: PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects. RESULTS: Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7-88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7-89.4), 53.9% (38.5-75.3), and 39.1% (25.2-60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0-95.3), 67.8% (50.9-90.3), and 58.9% (42.7-81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9-104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7-80.6), 53.2% (42.2-66.9), and 40.4% (29.6-55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5-99.1), 77.0% (64.4-92.0), and 67.1% (51.6-87.3). CONCLUSIONS: TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1425-1433, 2023.

Prognostic Impact of Tumor Immune Microenvironment and Its Predictive Role in Salivary Gland Cancer.

BACKGROUND: Recently, many studies have investigated the role of tumor immune microenvironment (TIME) in carcinogenesis, highlighting its relation to both tumor regression and progression. In particular, the "inflammatory system", made of innate and adaptive immune cells, interacts with cancer cells and their surrounding stroma. In this setting, the aim of this review is to summarize the current literature regarding the TIME of major salivary gland carcinomas (MSGCs), with particular attention on the characteristics and prognostic role of tumor infiltrating lymphocytes (TILs), the mechanisms that lead to TILs exhaustion and the important additional immune infiltrating factors that help SGC progression or remission. METHODS: A comprehensive literature search was performed concerning published articles on the role of TIME in MSGCs. RESULTS: In this work we summarize the advancing knowledge on TIME in SGCs by demonstrating the key prognostic and/or predictive value of specific immune features. CONCLUSION: From the analysis of the current 'status of the art' it clearly emerges a need for precise, unambiguous phenotyping of immune cell populations, as well as a more thorough understanding of the frequencies and interactions of multiple immune cell types inside the TIME and their spatial localization (intratumoral vs. stromal).