<i>Prognostic Significance of Tumor Infiltrating Lymphocytes in Melanoma</i>

Burton, Alison; Roach, Brent A.; Mays, Michael P.; Chen, Andrea F.; Ginter, Brooke; Vierling, Abbey M.; Scoggins, Charles R.; Martin, Robert C.G.; Stromberg, Arnold J.; Hagendoorn, Lee; McMasters, Kelly M.

doi:10.1177/000313481107700219

Cited by 85 publications

(50 citation statements)

References 17 publications

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“…The presence of TIL in neoplastic tissue is thought to indicate an anti-tumor immune response by the host and correlates with clinical outcome in several tumor types, especially in melanoma [ 28 , 29 ]. Dr. S. Rosenberg (SB, NIH, Bethesda, Maryland, US) was the first to demonstrate the anti-tumor activity of TIL in vivo in murine models in the 1980s of the past century [ 6 ].…”

Section: Adoptive Cell Therapy With Tumor-resident T Cellsmentioning

confidence: 99%

Adoptive cellular therapies: the current landscape

2018

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For many cancer types, the immune system plays an essential role in their development and growth. Based on these rather novel insights, immunotherapeutic strategies have been developed. In the past decade, immune checkpoint blockade has demonstrated a major breakthrough in cancer treatment and has currently been approved for the treatment of multiple tumor types. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) or gene-modified T cells expressing novel T cell receptors (TCR) or chimeric antigen receptors (CAR) is another strategy to modify the immune system to recognize tumor cells and thus carry out an anti-tumor effector function. These treatments have shown promising results in various tumor types, and multiple clinical trials are being conducted worldwide to further optimize this treatment modality. Most successful results were obtained in hematological malignancies with the use of CD19-directed CAR T cell therapy and already led to the commercial approval by the FDA. This review provides an overview of the developments in ACT, the associated toxicity, and the future potential of ACT in cancer treatment.

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Section: Adoptive Cell Therapy With Tumor-resident T Cellsmentioning

confidence: 99%

Adoptive cellular therapies: the current landscape

2018

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“…Tumor infiltrating lymphocytes (TIL) are believed to be a partial surrogate marker of the host anti-tumor immune response and are also thought to confer prognostic significance in melanoma. However, immunologic metrics have yet to be included in the melanoma American Joint Committee on Cancer (AJCC) staging system [ 7 – 11 ]. It is unclear whether age’s impact on the host immune response is reflected by TIL measurements.…”

Section: Introductionmentioning

confidence: 99%

Impact of aging on host immune response and survival in melanoma: an analysis of 3 patient cohorts

et al. 2016

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BackgroundAge has been reported as an independent prognostic factor for melanoma-specific survival (MSS). We tested the hypothesis that age impacts the host anti-tumor immune response, accounting for age-specific survival outcomes in three unique melanoma patient cohorts.MethodsWe queried the U.S. population-based Surveillance, Epidemiology, and End Results Program (SEER), the prospective tertiary care hospital-based Interdisciplinary Melanoma Cooperative Group (IMCG) biorepository, and the Cancer Genome Atlas (TCGA) biospecimen database to test the association of patient age at time of melanoma diagnosis with clinicopathologic features and survival outcomes. Age groups were defined as ≤45 (young), 46–65 (intermediate), and >65 (older). Each age group in the IMCG and TCGA cohorts was stratified by tumor infiltrating lymphocyte (TIL) measurements and tested for association with MSS. Differential expression of 594 immunoregulatory genes was assessed in a subset of primary melanomas in the IMCG and TCGA cohorts using an integrative pathway analysis.ResultsWe analyzed 304, 476 (SEER), 1241 (IMCG), and 292 (TCGA) patients. Increasing age at melanoma diagnosis in both the SEER and IMCG cohorts demonstrated a positive correlation with tumor thickness, ulceration, stage, and mortality, however age in the TCGA cohort did not correlate with mortality. Older age was associated with shorter MSS in all three cohorts. When the young age group in both the IMCG and TCGA cohorts was stratified by TIL status, there were no differences in MSS. However, older IMCG patients with brisk TILs and intermediate aged TCGA patients with high lymphocyte scores (3–6) had improved MSS. Gene expression analysis revealed top pathways (T cell trafficking, communication, and differentiation) and top upstream regulators (CD3, CD28, IFNG, and STAT3) that significantly changed with age in 84 IMCG and 43 TCGA primary melanomas.ConclusionsOlder age at time of melanoma diagnosis is associated with shorter MSS, however age’s association with clinicopathologic features is dependent upon specific characteristics of the study population. TIL as a read-out of the host immune response may have greater prognostic impact in patients older than age 45. Recognition of age-related factors negatively impacting host immune responses may provide new insights into therapeutic strategies for the elderly.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1026-2) contains supplementary material, which is available to authorized users.

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“…3,16 ). However, others published that TILs did not predict sur-vival 17 and there is no association of their presence and improved melanoma prognosis 11,[17][18][19] .…”

Section: Tils and Melanoma Stage And Prognosismentioning

confidence: 99%

Tumor infiltrating lymphocytes in malignant melanoma - allies or foes?

Židlík

Bezděková

Brychtová

2020

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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This is an overview of current problematics regarding the role of tumor infiltrating lymphocytes (TILs) in malignant melanomas. Various and often conflicting data have been published, correlating tumor type, stage, prognosis, as well as sex and age of patients. This is partly due to heterogeneity in scaling systems and unstandardized TILs grading but also due to changes of tumor-host interactions. Melanomas are an immunologically heterogeneous group with variability of TILs, where distinct gene expression patterns were found in tumors with absent, and/or non-brisk TIL grade versus brisk TIL grade. However, the presence of TILs alone appears to be inadequate for implicating them as immunologically functional. Further characterisation of TIL phenotype and function is warranted. This especially concerns, evaluation of TILs of the suppressor phenotype but rather than as a prognostic factor, more for prediction of targeted immunotherapy.

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Prognostic Significance of Tumor Infiltrating Lymphocytes in Melanoma

Cited by 85 publications

References 17 publications

Adoptive cellular therapies: the current landscape

Adoptive cellular therapies: the current landscape

Impact of aging on host immune response and survival in melanoma: an analysis of 3 patient cohorts

Tumor infiltrating lymphocytes in malignant melanoma - allies or foes?

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