Dataset Information

Role of tumor-infiltrating lymphocytes in melanoma prognosis and treatment strategies: A systematic review and meta-analysis.

ABSTRACT:

Purpose

Numerous studies underscore the relevance of tumor-infiltrating-lymphocytes (TILs) as important prognostic factors for melanoma. This meta-analysis aims to provide a comprehensive literature overview elucidating their role in predicting patient outcomes, specifically investigating the association between TIL density and prognosis.

Methods

From an initial pool of 6094 records, 16 met the eligibility criteria, encompassing a collective cohort of 16021 patients. Data on TIL counts, clinical characteristics, and survival metrics (5-year overall survival [5yOS], 10-year overall survival [10yOS], and 5-year melanoma-specific survival [5yMSS]) were extracted from each study and expressed as proportions. Results were graphically presented using forest plots, reporting the estimates from individual studies, summary estimates, and corresponding 95 % confidence intervals (CI).

Results

Analysis revealed a statistically significant difference in 5yOS concerning subgroup differences However, 10yOS and 5yMSS did not exhibit statistical significance. Nonetheless, a consistent trend emerged indicating a higher survival rate corresponding to increased immune cell density, ranging from absent TILs to brisk levels.

Conclusions

TILs present potential as a readily applicable prognostic factor. Yet, further investigations into their density and phenotypic subpopulation characteristics could enhance our understanding of their predictive value in tailoring optimal patient-specific therapies.

SUBMITTER: Garutti M

PROVIDER: S-EPMC11341338 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Publications

Role of tumor-infiltrating lymphocytes in melanoma prognosis and treatment strategies: A systematic review and meta-analysis.

Garutti Mattia M Bruno Rachele R Polesel Jerry J Pizzichetta Maria Antonietta MA Puglisi Fabio F

Heliyon 20240606 12

<h4>Purpose</h4>Numerous studies underscore the relevance of tumor-infiltrating-lymphocytes (TILs) as important prognostic factors for melanoma. This meta-analysis aims to provide a comprehensive literature overview elucidating their role in predicting patient outcomes, specifically investigating the association between TIL density and prognosis.<h4>Methods</h4>From an initial pool of 6094 records, 16 met the eligibility criteria, encompassing a collective cohort of 16021 patients. Data on TIL c ...[more]

PMID: 39183829

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Project description:Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the importance of a deeper understanding of the special tumor microenvironment of CCA and the role of immune cells interacting with the tumor. Tumor-infiltrating lymphocytes (TILs) are an important component of the adaptive immune system and the foundation of current immunotherapy. Therefore, the aim of this systemic review is to summarize the current literature focusing on the proportions and distribution, molecular pathogenesis, prognostic significance of TILs and their role in immunotherapy for CCA patients.In CCA, CD8+ and CD4+ T lymphocytes represent the majority of TILs and are mostly sequestered around the cancer cells. CD20+ B lymphocytes and Natural Killer (NK) cells are less frequent. In contrast, Foxp3+ cells (regulatory T cells, Tregs) are observed to infiltrate into the tumor. In the immune microenvironment of CCA, cancer cells and stromal cells such as TAMs, TANs, MSDCs and CAFs inhibit the immune protection function of TILs by secreting factors like IL-10 and TGF-β. With respect to molecular pathogenesis, the Wnt/-catenin, TGF-signaling routes, aPKC-i/P-Sp1/Snail Signaling, B7-H1/PD-1Pathway and Fas/FasL signaling pathways are connected to the malignant potential and contributed to tumor immune evasion by increasing TIL apoptosis. Distinct subtypes of TILs show different prognostic implications for the long-term outcome in CCA. Although there are occasionally conflicting results, CD8+ and CD4+ T cells, and CD20+ B cells are positively correlated with the oncological prognosis of CCA, while a high number of Tregs is very likely associated with worse overall survival. TILs also play a major role in immunotherapy for CCA.In summary, the presence of TILs may represent an important marker for the prognosis and a potential target for novel therapy, but more clinical and translationaldata is needed to fully unravel the importance of TILs in the treatment of CCA.

Project description:BackgroundThe predictive value of tumor-infiltrating lymphocytes (TILs) in immune-related adverse event (irAE) development remains unknown, although an association between tumor immunogenicity and irAEs has been suggested. We investigated the association between TIL abundance in pretreatment primary and metastasis specimens and the subsequent development of severe irAEs.Patients and methodsWe retrospectively identified patients with advanced cutaneous melanoma who received first-line anti-programmed cell death protein 1 (PD-1) with or without anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) from 10 hospitals in the Netherlands. TILs were scored on representative hematoxylin and eosin (H&E) stains of the primary melanoma and pretreatment melanoma metastasis as 'absent', 'nonbrisk', or 'brisk'. A univariable logistic regression analysis was carried out to assess the association between the TIL scores and the development of severe irAEs. Fine and Gray subdistribution hazard models were used to estimate the cumulative incidence of severe irAEs.ResultsOf the 1346 eligible patients, 536 patients had primary melanoma specimens available, and 613 patients had metastasis specimens available. Severe irAEs occurred in 15% of anti-PD-1-treated patients and 49% of anti-PD-1 + anti-CTLA-4-treated patients. The presence of TILs was not associated with the occurrence of grade ≥3 irAEs in primary melanoma specimens (P = 0.70) nor pretreatment metastasis specimens (P = 0.91). In the univariable analysis, patients with brisk TILs did not have a higher chance of developing severe irAEs compared with patients with absent TILs, for both primary specimen (odds ratio 1.15, 95% confidence interval 0.60-2.18) and metastasis specimen (odds ratio 0.77, 95% confidence interval 0.37-1.59). There was also no significant difference in the lifetime risk or timing of the development of severe irAEs in patients with TILs present compared with patients with TILs absent.ConclusionThere was no association between the TIL scores on H&E-stained slides from the primary melanoma or pretreatment metastasis and the development of grade 3 or higher irAEs. Additionally, no correlation was found between the presence of TILs and the timing of irAEs.

Dataset Information

Role of tumor-infiltrating lymphocytes in melanoma prognosis and treatment strategies: A systematic review and meta-analysis.

Purpose

Methods

Results

Conclusions

Publications

Role of tumor-infiltrating lymphocytes in melanoma prognosis and treatment strategies: A systematic review and meta-analysis.

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