Lymphoid infiltration as a predictor of successful immunotherapy with melanoma

Titov, Konstantin; Chikileva, Irina O.; Киселевский, М. В.; Казаков, А. М.

doi:10.18027/2224-5057-2017-1-61-66

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…Однако не все пациенты с меланомой имеют данные мутации и, соответственно, мишени для таргетной терапии [2]. Для группы пациентов с отсутствием мишеней для использующейся в настоящий момент таргетной терапии, низкой экспрессией рецепторов и прогностически неблагоприятным количественным и качественным составом лимфоидной инфильтрации для успешного применения ингибиторов иммунных контрольных точек [3,4] необходим поиск иных подходов к лечению, в частности выявление новых точек приложения таргетной терапии.…”

Section: оригинальные статьиunclassified

Expression rate of ALK tyrosine kinase and TAG-72 oncoprotein in primary skin melanoma

Titov¹,

Ротин²,

Казаков³

et al. 2018

Rossijskij bioterapevtičeskij žurnal

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Objective.Determine the frequency of occurrence of tyrosine kinase expression of the mutated ALK and TAG-72 gene among patients with primary melanoma of the skin, to identify their association with a number of histological parameters, and to assess the diagnostic value of the determination of ALK and TAG-72.Materials and methods.Paraffin blocks with surgical material from 40 patients with primary skin melanoma. For routine histological examination, the material was fixed with 10 % neutral formalin for 24 h, poured into paraffin, sections were prepared with a thickness of 4–5 μm, stained with hematoxylin and eosin. IHC study with monoclonal antibodies D57.3 to ALK was performed on an immunostender – Ventana, with antibodies B72.3 to TAG-72 – on Thermo Fischer. As a detection system used: Envision – for TAG-72 and Ventana – for ALK.Results.ALK mutation was detected in 7 (12 %), TAG-72 – 4 (10 %) cases. Evaluation of the correlation force between the presence of ALK and TAG-72 showed a direct average coupling strength (correlation coefficient was 0.31). A direct correlation of the mean force between the presence of TAG-72 oncoprotein, ALK mutation and ulceration in the patient was found – the correlation coefficient was 0.53 and 0.68, respectively. There was a statistically significant association between the presence of ALK and lymphoid infiltration, which in most cases (57 %) was pronounced (p <0.05).Conclusion.Comparing the positive sign of the expression of ALK – 17.5 % and TAG-72 – 10 %, and the positive of their simultaneous detection – 7.5 %, it can be concluded that further studies to determine their diagnostic value are promising. The presence of severe lymphoid infiltration in ALK-positive patients claims a diagnostic value in primary skin melanoma.

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Section: оригинальные статьиunclassified

Expression rate of ALK tyrosine kinase and TAG-72 oncoprotein in primary skin melanoma

Titov¹,

Ротин²,

Казаков³

et al. 2018

Rossijskij bioterapevtičeskij žurnal

Self Cite

View full text Add to dashboard Cite

show abstract

Prognosis and treatment of HIV-associated malignant skin tumors

Titov¹,

Gomberg²,

Neretin³

et al. 2022

Klin. dermatol. venerol.

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Role of immunohistochemical prognostic factors in various types of immunotherapy for metastatic melanoma: A retro-prospective study

Oganesyan,

Zavalishina,

Ognerubov

et al. 2024

J. Mod. Onco.

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Background. Anti-PD-1 immunotherapy (IT) is the standard of care for patients with metastatic melanoma. However, in the real world, IT is effective only in a fraction of patients. The lack of valid prognostic factors for various immunotherapy agents warrants a comprehensive and advanced study of this topic. Aim. To improve the outcomes of the first-line therapy for disseminated melanoma based on identifying immunohistochemical predictors of IT efficacy. Materials and methods. Data from 130 patients who were treated with immune checkpoint inhibitors nivolumab or prolgolimab in the first-line therapy for disseminated melanoma between 2017 and 2024 were analyzed. Results. The expression of PD-L110 on tumor cells was found to be a predictor of effective therapy: in the nivolumab group, the 2-year disease-free survival (DFS) with PD-L1 level 10% was high at 79% (95% confidence interval – CI 61–100); the 1-year DFS was 89% (95% CI 78–100) compared to 17% (95% CI 3.2–88) with a lower level of PD-L1 expression (p0.0001). In the prolgolimab group, the 2-year DFS with PD-L110% was also high at 78% (p0.0001; CI 54–100), the 1-year DFS was 94% (95% CI 84–100) compared to 35% (95% CI 17–73) with a lower level of PD-L1 expression (p0.0001). A less severe course of the disease was observed in patients with both peritumoral and intratumoral locations versus those with only peritumoral locations of the immune infiltrate. The study of the presence and form of lymphoid infiltration of the tumor showed the following direct relationship: in the nivolumab group, the 2-year DFS was 94% (95% CI 83–100) compared to 8.3% (95% CI 1.3–54), in the prolgolimab group, the 1-year DFS was 82% (95% CI 68–100) compared to 15% (95% CI 2.6–86); p0.0001. It was found that the predominance of CD8+ over CD4+ is associated with better results of IT: in the nivolumab group, the 2-year DFS was 87% (95% CI 74–100) compared to 19% (95% CI 4–91) in the absence of CD8+ predominance over CD4+; in the prolgolimab group, the 2-year DFS was 73% (95% CI 51–100) in patients with CD8+ predominance over CD4+ (p=0.0001). In patients without CD8 predominance over CD4, 2-year DFS was not achieved. The one-year DFS was 85% (95% CI 70–100) and 25% (95% CI 8.4–76), respectively; p=0.0001. Conclusion. The results of the study suggest that immunohistochemical characteristics such as a PD-L1 expression level 10%, the simultaneous presence of peri- and intratumoral lymphoid infiltration of the tumor, the ratio of the intensity of lymphoid infiltration with tumor-infiltrating lymphocytes (TILs), and the predominance of CD8+ over CD4+ can be considered predictors of IT efficacy with nivolumab and prolgolimab.

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Lymphoid infiltration as a predictor of successful immunotherapy with melanoma

Cited by 3 publications

References 24 publications

Expression rate of ALK tyrosine kinase and TAG-72 oncoprotein in primary skin melanoma

Expression rate of ALK tyrosine kinase and TAG-72 oncoprotein in primary skin melanoma

Prognosis and treatment of HIV-associated malignant skin tumors

Role of immunohistochemical prognostic factors in various types of immunotherapy for metastatic melanoma: A retro-prospective study

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