Expression of TILs and Patterns of Gene Expression from Paired Samples of Malignant Pleural Mesothelioma (MPM) Patients

被引:0
作者
Cedres, Susana [1 ]
Serna, Garazi [2 ]
Gonzalez-Medina, Alberto [3 ]
Valdivia, Augusto [1 ]
Assaf-Pastrana, Juan David [1 ]
Iranzo, Patricia [1 ]
Callejo, Ana [1 ]
Pardo, Nuria [1 ]
Navarro, Alejandro [1 ]
Martinez-Marti, Alex [1 ]
Priano, Ilaria [1 ]
Fasani, Roberta [2 ]
Guardia, Xavier [2 ]
Gonzalo, Javier [4 ]
Carbonell, Caterina [5 ]
Frigola, Joan [5 ]
Amat, Ramon [5 ]
Navarro, Victor [6 ]
Dienstmann, Rodrigo [6 ]
Vivancos, Ana [3 ]
Nuciforo, Paolo [2 ]
Felip, Enriqueta [1 ]
机构
[1] Hosp Univ Vall dHebron, Vall dHebron Inst Oncol VHIO, Barcelona 08035, Spain
[2] Vall dHebron Inst Oncol VHIO, Mol Oncol Grp, Barcelona 08035, Spain
[3] Vall dHebron Inst Oncol VHIO, Canc Genom Lab, Barcelona 08035, Spain
[4] Vall dHebron Inst Oncol VHIO, Barcelona 08035, Spain
[5] Vall dHebron Inst Oncol VHIO, Clin Res Dept, Passeig Vall dHebron 119-129, Barcelona 08035, Spain
[6] Vall dHebron Inst Oncol VHIO, Oncol Data Sci Grp, Barcelona 08035, Spain
关键词
malignant pleural mesothelioma; immunotherapy; gene expression; TIL; TUMOR-INFILTRATING LYMPHOCYTES; IMMUNE MICROENVIRONMENT; CHRONIC INFLAMMATION; OPEN-LABEL; CISPLATIN; IMPACT; CANCER; CELLS;
D O I
10.3390/cancers15143611
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary Recently immunotherapy has been approved in first line for patients with MPM. However, the benefit of immunotherapy in MPM is modest, and recognizing the immune landscape of this tumor could guide the optimal therapeutic strategy. In some tumors dynamic changes of TILs has been reported after chemotherapy, endocrine therapy and immunotherapy. We investigated the changes in expression of TILs in human MPM tumor tissue using immunohistochemistry and patterns of gene expression from paired samples. We included samples of patients treated with chemotherapy, immunotherapy and patients without any treatment between the samples. In our series, after systemic treatment or at progressive disease we observed a decrease of the number of TILs and a downregulation of the immune-related genes. In patients without any treatment between the samples we found an increase of immune cells. We suggest that the immune system tends to turn off during the evolution of disease of after treatment. MPM is an aggressive disease with an immunosuppressive tumor microenvironment, and interest in exploring immunotherapy in this disease has been increasing. In the first line of treatment, the combination of nivolumab and ipilimumab demonstrated an improvement in survival over chemotherapy. The presence of TILs has been recognized as a marker of antitumor immune response to chemotherapy in solid tumors. The aim of our study is to identify the effect of treatment on immune cells and the immune gene profile in MPM. We investigated the changes in expression of TILs in 10 human MPM paired tumor tissues using immunohistochemistry and gene expression analysis from paired untreated and treated samples. In this small series, we demonstrated that during the evolution of disease without any treatment there was an increase in the inflammatory component in tumor samples. After systemic treatment there was a decrease in the number of TILs. We observed that after systemic treatment or disease progression immune gene signatures were suppressed. Our integrated analysis of paired samples with immune profile and genomic changes on MPM suggested that during the evolution of the disease the immune system tends to switch, turning off with treatment.
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页数:17
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共 51 条
  • [1] [Anonymous], 2023, NCCN GUID VERS 1
  • [2] Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma
    Anraku, Masaki
    Cunningham, Kristopher S.
    Yun, Zhihong
    Tsao, Ming-Sound
    Zhang, Li
    Keshavjee, Shaf
    Johnston, Michael R.
    de Perrot, Marc
    [J]. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2008, 135 (04) : 823 - 829
  • [3] First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial
    Baas, Paul
    Scherpereel, Arnaud
    Nowak, Anna K.
    Fujimoto, Nobukazu
    Peters, Solange
    Tsao, Anne S.
    Mansfield, Aaron S.
    Popat, Sanjay
    Jahan, Thierry
    Antonia, Scott
    Oulkhouir, Youssef
    Bautista, Yolanda
    Cornelissen, Robin
    Greillier, Laurent
    Grossi, Francesco
    Kowalski, Dariusz
    Rodriguez-Cid, Jeronimo
    Aanur, Praveen
    Oukessou, Abderrahim
    Baudelet, Christine
    Zalcman, Gerard
    [J]. LANCET, 2021, 397 (10272) : 375 - 386
  • [4] Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications
    Blum, Yuna
    Meiller, Clement
    Quetel, Lisa
    Elarouci, Nabila
    Ayadi, Mira
    Tashtanbaeva, Danisa
    Armenoult, Lucile
    Montagne, Francois
    Tranchant, Robin
    Renier, Annie
    de Koning, Leanne
    Copin, Marie-Christine
    Hofman, Paul
    Hofman, Veronique
    Porte, Henri
    Le Pimpec-Barthes, Francoise
    Zucman-Rossi, Jessica
    Jaurand, Marie-Claude
    de Reynies, Aurelien
    Jean, Didier
    [J]. NATURE COMMUNICATIONS, 2019, 10 (1)
  • [5] Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations
    Bueno, Raphael
    Stawiski, Eric W.
    Goldstein, Leonard D.
    Durinck, Steffen
    De Rienzo, Assunta
    Modrusan, Zora
    Gnad, Florian
    Nguyen, Thong T.
    Jaiswal, Bijay S.
    Chirieac, Lucian R.
    Sciaranghella, Daniele
    Dao, Nhien
    Gustafson, Corinne E.
    Munir, Kiara J.
    Hackney, Jason A.
    Chaudhuri, Amitabha
    Gupta, Ravi
    Guillory, Joseph
    Toy, Karen
    Ha, Connie
    Chen, Ying-Jiun
    Stinson, Jeremy
    Chaudhuri, Subhra
    Zhang, Na
    Wu, Thomas D.
    Sugarbaker, David J.
    de Sauvage, Frederic J.
    Richards, William G.
    Seshagiri, Somasekar
    [J]. NATURE GENETICS, 2016, 48 (04) : 407 - +
  • [6] Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease
    Camacho, Jessica
    Rabano, Alberto
    Marazuela, Paula
    Bonaterra-Pastra, Anna
    Serna, Garazi
    Moline, Teresa
    Ramon y Cajal, Santiago
    Martinez-Saez, Elena
    Hernandez-Guillamon, Mar
    [J]. BRAIN PATHOLOGY, 2022, 32 (01)
  • [7] Molecular Pathways: Targeting Mechanisms of Asbestos and Erionite Carcinogenesis in Mesothelioma
    Carbone, Michele
    Yang, Haining
    [J]. CLINICAL CANCER RESEARCH, 2012, 18 (03) : 598 - 604
  • [8] Changes of tumor infiltrating lymphocyte subtypes before and after neoadjuvant endocrine therapy in estrogen receptor-positive breast cancer patients - an immunohistochemical study of cd8+and foxp3+using double immunostaining with correlation to the pathobiological response of the patients
    Chan, Monica S. M.
    Wang, Lin
    Felizola, Saulo J. A.
    Ueno, Takayuki
    Toi, Masakazu
    Loo, W.
    Chow, Louis W. C.
    Suzuki, Takashi
    Sasano, Hironobu
    [J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS, 2012, 27 (04) : E295 - E304
  • [9] Evaluating the effect of immune cells on the outcome of patients with mesothelioma
    Chee, Serena J.
    Lopez, Maria
    Mellows, Toby
    Gankande, Sharmali
    Moutasim, Karwan A.
    Harris, Scott
    Clarke, James
    Vijayanand, Pandurangan
    Thomas, Gareth J.
    Ottensmeier, Christian H.
    [J]. BRITISH JOURNAL OF CANCER, 2017, 117 (09) : 1341 - 1348
  • [10] Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet?
    Coussens, Lisa M.
    Zitvogel, Laurence
    Palucka, A. Karolina
    [J]. SCIENCE, 2013, 339 (6117) : 286 - 291