bims-tuinly Biomed News
on Tumor-infiltrating lymphocytes therapy
Issue of 2025–02–23
six papers selected by
Pierpaolo Ginefra, Ludwig Institute for Cancer Research
  1. Peripheral Immune Biomarkers Associated with Response to Adoptive Cell Therapy with Tumor Infiltrating Lymphocytes.
  2. The Prognostic Significance of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Supraglottic Laryngeal Squamous Cell Carcinoma.
  3. The impact of MITF expression on tumor-infiltrating lymphocytes in melanoma: Insights into immune microenvironment dynamics.
  4. Is It Unnecessary to Assess Tumor Stroma-Infiltrating Lymphocytes in Localized Lung Adenocarcinomas?
  5. OUTCOMES OF TUMOR-INFILTRATING LYMPHOCYTE THERAPY IN SOLID TUMOURS - A SYSTEMATIC REVIEW AND META ANALYSIS.
  6. Tumor infiltrating lymphocytes in primary melanoma are associated with a better prognosis.
  1. Clin Exp Immunol. 2025 Feb 18. pii: uxaf010. [Epub ahead of print]
    Peripheral Immune Biomarkers Associated with Response to Adoptive Cell Therapy with Tumor Infiltrating Lymphocytes.
    Cecilie Oelvang Madsen, Marta Velasco Santiago, Evelina Martinenaite, Troels Holz Borch, Marco Donia, Inge Marie Svane, Morten Hansen.
      Adoptive cell therapy (ACT) with ex-vivo expanded tumor-infiltrating lymphocytes (TILs, TIL-ACT) has shown clinical efficacy in a significant proportion of patients with metastatic melanoma. To further target TIL-ACT towards responsive patients, identifying predictive biomarkers and understanding broader immune dynamics remain critical. This study investigated the peripheral blood immune landscape in 47 patients with metastatic melanoma undergoing TIL-ACT, assessing antitumor reactivity and peripheral immune cell profiles before and after treatment. Responders displayed increased frequency of circulating tumor-reactive cells post-treatment, and higher baseline levels of activated CD57-expressing T cells, serving as potential biomarkers of response. In contrast, persistent high serum levels of interleukin (IL)-6 and IL-8, higher frequencies of CD38-expressing T cells and regulatory T cells (Tregs) post-treatment, correlated with unfavorable outcomes. These findings contribute to understanding of the peripheral immune landscape associated with response to TIL-ACT, offering valuable insights into predictive biomarkers and mechanisms to improve patient selection.
    Keywords:  adoptive cell therapy; biomarkers; immune monitoring; metastatic melanoma; tumor infiltrating lymphocytes (TILs)
    DOI:  https://doi.org/10.1093/cei/uxaf010
  2. APMIS. 2025 Feb;133(2): e70005
    The Prognostic Significance of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Supraglottic Laryngeal Squamous Cell Carcinoma.
    Elvir Zvrko, Muhedin Kadic, Ljiljana Vuckovic.
      Laryngeal squamous cell carcinoma (LSCC) is characterized by diverse profiles of tumor-infiltrating lymphocytes (TILs). We aimed to investigate the potential prognostic role of TILs and programmed death-ligand 1 (PD-L1) in patients with supraglottic LSCC. The expression of PD-L1 and TILs was assessed using immunohistochemistry in 39 patients with primary supraglottic LSCC and correlated with clinicopathological characteristics and disease-free survival (DFS). Survival curves were measured using the Kaplan-Meier method, and differences in survival between the groups were estimated using the log-rank test. TIL density was significantly higher in PD-L1-positive (combined positive score: CPS ≥ 1) than in PD-L1-negative (CPS < 1) patients (p = 0.000). Lower PD-L1 expression was significantly associated with a locoregional recurrence (Fisher's exact test, p = 0.008). DFS was significantly longer in patients with CPS ≥ 1 than in those with CPS < 1 (Log-rank test, p = 0.004). Multivariate Cox regression analysis showed that a low CPS (p = 0.003) and positive nodal status (p = 0.012) were statistically significant and independent predictors of malignancy recurrence. PD-L1 represents a valuable marker for predicting recurrence and shorter survival after definitive therapy.
    Keywords:  PDL1; laryngeal squamous cell carcinoma; prognostic biomarkers; supraglottis; tumor‐infiltrating lymphocytes
    DOI:  https://doi.org/10.1111/apm.70005
  3. Biomol Biomed. 2025 Feb 18.
    The impact of MITF expression on tumor-infiltrating lymphocytes in melanoma: Insights into immune microenvironment dynamics.
    Damir Vučinić, Matea Lekić, Gordana Žauhar, Gordana Zamolo.
      Melanoma progression is influenced by complex interactions between tumor cells and the immune microenvironment. This study examined the relationship between microphthalmia-associated transcription factor (MITF) expression and the immune microenvironment in primary melanoma using a modified classification of tumor-infiltrating lymphocytes (TILs) based on conventional BRISK categories. Archival formalin-fixed, paraffin-embedded tissue samples from 81 primary melanoma patients were analyzed via tissue microarray immunohistochemistry to assess MITF protein levels. TIL patterns were categorized into six groups, refining the traditional BRISK classification to distinguish between continuous and discontinuous infiltration, as well as peripheral vs intratumoral distribution. The analysis revealed that melanomas classified under the BRISK B category exhibited the highest MITF expression, often exceeding 50%. In contrast, tumors in the NON-BRISK and ABSENT TIL groups showed significantly lower MITF expression (mean values: 32.73% ± 16.98% and 22.00% ± 10.54%, respectively), with statistically significant differences (Kruskal-Wallis test, P = 0.027; modified classification, P = 0.011). Additionally, the presence of CD20+ B lymphocytes correlated with increased MITF expression (P = 0.009). MITF gene amplification was detected in 29% of cases, though its association with protein expression showed only a trend (P = 0.058). These findings highlight the complex interplay between MITF expression and TIL distribution in melanoma, suggesting that refined TIL classification may offer deeper insights into tumor immunobiology and help predict responses to immunotherapy.
    DOI:  https://doi.org/10.17305/bb.2025.12125
  4. Tanaffos. 2024 Feb;23(2): 129-138
    Is It Unnecessary to Assess Tumor Stroma-Infiltrating Lymphocytes in Localized Lung Adenocarcinomas?
    Mona Mlika, Abir Rais, Omar El Mnif, Chokri Haddouchi, Mehdi Abdennadher, Rahma Ayadi, Emna Braham, Olfa Ismail, Adel Marghli, Faouzi Mezni.
       Background: During the last decade, more attention was paid to the tumor cell microenvironment, especially to tumor stroma-infiltrating lymphocytes (TILs). This study aimed to assess the prognostic impact of different TILs subpopulations and PD-L1 positive tumor cells in localized lung adenocarcinomas.
    Materials and Methods: We conducted a retrospective descriptive study, which included localized adenocarcinomas diagnosed in the department of pathology and resected in the Thoracic Surgery Department of the same hospital between 2015 and 2020. TILs were analyzed using the immunohistochemical method for Fox-P3, CD4, CD8, CD20, and CD3. Besides, the PD-L1 antibody was used to assess tumor cell expression. Intra-tumoral and stromal labeled lymphocytes were quantified by manual counting at high magnification (X400). Fox-P3+/CD8+, Fox-P3+/CD4+, FoxP3+/PD-L1+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of TILs was assessed with respect to overall survival (OS) and recurrence free survival (ReFS).
    Results: A total of 44 localized adenocarcinomas were included. In the univariate analysis, the prognostic factors influencing OS included gender, adenocarcinoma subtype, Tumor-Infiltrating Lymphocyte (TIL) score, TIL grade, PD-L1 expression, PD-L1 grade, tumor immunity in the microenvironment, and the expressions of various immune markers: CD3, CD4, CD8, CD20, and FoxP3. The analysis also considered the FoxP3 ratio, FIL score, and different ratios involving immune markers, such as CD8/CD4 ratio, FoxP3/CD8 ratio, FoxP3/CD4 ratio, and FoxP3/PD-L1 ratio. The prognostic factors influencing the ReFS consisted of gender, the adenocarcinoma subtype, TIL score, TIL grade, PD-L1, PD-L1 grade, TIM, CD8 expression, CD20 expression, FIL score, Fox-P3/CD8 ratio, Fox-P3/CD4 ratio, and Fox-P3/PD-L1 ratio. Multivariate analysis revealed no independent predictive factors of OS or ReFS.
    Conclusion: Despite the limitations of this study, the results highlighted that TILs may not represent an independent prognostic factor in localized adenocarcinomas and don't play a major role in comparison to the tumor stage.
    Keywords:  Tumor stroma-infiltrating lymphocytes; adenocarcinomas; immunohistochemistry; lung cancer; prognosis
  5. Crit Rev Oncol Hematol. 2025 Feb 18. pii: S1040-8428(25)00059-9. [Epub ahead of print] 104671
    OUTCOMES OF TUMOR-INFILTRATING LYMPHOCYTE THERAPY IN SOLID TUMOURS - A SYSTEMATIC REVIEW AND META ANALYSIS.
    Ullas Mony, Vishnu Priya Veeraraghavan.
       BACKGROUND: Tumor-infiltrating lymphocyte (TIL) treatment is an individualized method of treating different types of solid tumors by using the immune system of the body to target and destroy cancer cells. Although its usefulness has been shown in certain diseases, such as ovarian cancer and melanoma, research is still being done to see whether it is also beneficial against a wider variety of solid tumors.
    AIM: To methodically assess the safety, effectiveness, and clinical results of TIL therapy for various solid tumors.
    METHODOLOGY: A thorough search in various databases produced 218 papers on TIL treatment for various solid tumors (2018-2024). Nine of the ten papers that satisfied the requirements for inclusion in the quantitative analysis were also included in the systematic review. Two reviewers separately extracted the data and evaluated it. The Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool were used to evaluate the quality of the studies, and the I2 statistic in the meta-analysis was used to measure heterogeneity.
    RESULTS: Numerous studies that looked at the effectiveness of TIL treatment in different types of cancer showed different results. In NSCLC and melanoma, higher CD8+/CD4+ TIL ratios were associated with improved outcomes; in advanced melanoma, TIL therapy was superior to ipilimumab. Response rates differed, with NSCLC showing up at 23.1% and melanoma up to 53.3%. Most studies were of good quality and is confirmed by the Newcastle-Ottawa Scale, while some had problems with follow-up. The results' dependability was confirmed by the ROBINS-I and ROB2 tools, which showed low to moderate bias risk.
    CONCLUSION: According to the study's findings, TIL therapy is effective in treating solid tumors, especially melanoma, but its results vary according to the kind of cancer as well as tumour microenvironments. Therefore more research is needed to determine the best course of action.
    Keywords:  Cancer Immunotherapy; Disease-Specific Survival; Melanoma; Non-Small Cell Lung Cancer; Solid Tumors; Squamous Cell Carcinoma; Tumor Microenvironment
    DOI:  https://doi.org/10.1016/j.critrevonc.2025.104671
  6. Am J Surg. 2025 Feb 08. pii: S0002-9610(25)00065-0. [Epub ahead of print] 116243
    Tumor infiltrating lymphocytes in primary melanoma are associated with a better prognosis.
    Sentinel Lymph Node Working Group
       BACKGROUND: The relationship between tumor infiltrating lymphocytes (TIL) and survival in melanoma is poorly understood. We present a large multicenter study assessing the association between TIL and survival.
    METHODS: The Sentinel Lymph Node Working Group database was queried from 1993 to 2024 for cases with known TIL and survival data. TIL was analyzed dichotomously and stratified as non-brisk, brisk, and absent. Clinicopathologic factors were correlated with melanoma-specific survival (MSS), overall survival (OS), and recurrence-free survival (RFS).
    RESULTS: Among 4957 patients, TIL was present in 3980 (80.2 ​%) of patients. TIL was prognostic of MSS (p ​= ​0.0033), OS (p ​= ​0.0053), and RFS (p ​= ​0.0011). In the stratified analysis, brisk TIL was more strongly associated with MSS, OS, and RFS than non-brisk TIL (all p ​< ​0.04). Among patients with a positive sentinel lymph node, TIL was prognostic of MSS, OS, and RFS (all p ​< ​0.03).
    CONCLUSIONS: TIL is strongly predictive of survival in melanoma and may be useful in risk stratification when deciding whether risks of adjuvant therapy outweigh benefits for certain patients.
    Keywords:  Melanoma; Melanoma-specific survival; Overall survival; Recurrence-free survival; Sentinel lymph node biopsy; Staging; TIL; Tumor infiltrating lymphocytes
    DOI:  https://doi.org/10.1016/j.amjsurg.2025.116243
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