Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center

被引:1
作者
Yee, Elliott J. [1 ]
Gilbert, Danielle [1 ]
Kaplan, Jeffrey [2 ]
Wani, Sachin [3 ]
Kim, Sunnie S. [4 ]
McCarter, Martin D. [1 ]
Stewart, Camille L. [1 ]
机构
[1] Univ Colorado, Dept Surg, Div Surg Oncol, Anschutz Med Campus, Aurora, CO 80045 USA
[2] Univ Colorado, Dept Pathol, Aurora, CO 80045 USA
[3] Univ Colorado, Dept Med, Div Gastroenterol, Aurora, CO 80045 USA
[4] Univ Colorado, Dept Med, Div Med Oncol, Aurora, CO 80045 USA
关键词
gastric cancer; tumor-infiltrating lymphocytes; neoadjuvant chemotherapy; immunotherapy; CELL; METASTASIS; ADENOCARCINOMA; EPIDEMIOLOGY; MULTICENTER; NIVOLUMAB; DOCETAXEL; SURVIVAL;
D O I
10.3390/cancers16071428
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary In this investigation, we analyzed the number, type, and location of immune cells within surgically resected gastric cancer specimens treated with or without preoperative chemotherapy. We hypothesized that chemotherapy can stimulate the host immune system, as evidenced by an increased number of anti-tumor infiltrating lymphocytes in the tumor microenvironment. We found significantly elevated levels of immune cells within chemotherapy-treated tumors compared with chemotherapy-naive specimens. We also revealed important associations between survival and immune lymphocytes in the tumor-related stromal tissue. Together, we added evidence supporting the immunostimulatory role of chemotherapy and underscore the potential utility of immunotherapy in resectable gastric cancer.Abstract Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles, as evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, as well as total TILs (CD4+, CD8+, Treg, B cells), within chemotherapy-treated tumors compared with chemotherapy-naive specimens. We also revealed important associations between survival and pathologic responses with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherapy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer.
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页数:14
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共 49 条
[1]   Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial [J].
Al-Batran, Salah-Eddin ;
Hofheinz, Ralf D. ;
Pauligk, Claudia ;
Kopp, Hans-Georg ;
Haag, Georg Martin ;
Luley, Kim Barbara ;
Meiler, Johannes ;
Homann, Nils ;
Lorenzen, Sylvie ;
Schmalenberg, Harald ;
Probst, Stephan ;
Koenigsmann, Michael ;
Egger, Matthias ;
Prasnikar, Nicole ;
Caca, Karel ;
Trojan, Joerg ;
Martens, Uwe M. ;
Block, Andreas ;
Fischbach, Wolfgang ;
Mahlberg, Rolf ;
Clemens, Michael ;
Illerhaus, Gerald ;
Zirlik, Katja ;
Behringer, Dirk M. ;
Schmiegel, Wolff ;
Pohl, Michael ;
Heike, Michael ;
Ronellenfitsch, Ulrich ;
Schuler, Martin ;
Bechstein, Wolf O. ;
Koenigsrainer, Alfred ;
Gaiser, Timo ;
Schirmacher, Peter ;
Hozaeel, Wael ;
Reichart, Alexander ;
Goetze, Thorsten O. ;
Sievert, Mark ;
Jaeger, Elke ;
Moenig, Stefan ;
Tannapfel, Andrea .
LANCET ONCOLOGY, 2016, 17 (12) :1697-1708
[2]  
American Cancer Society Cancer Facts & Figures, 2024, Stomach Cancer Survival Rates: American Cancer Society
[3]   Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study [J].
Bang, Yung-Jue ;
Kang, Yoon-Koo ;
Catenacci, Daniel V. ;
Muro, Kei ;
Fuchs, Charles S. ;
Geva, Ravit ;
Hara, Hiroki ;
Golan, Talia ;
Garrido, Marcelo ;
Jalal, Shadia I. ;
Borg, Christophe ;
Doi, Toshihiko ;
Yoon, Harry H. ;
Savage, Mary J. ;
Wang, Jiangdian ;
Dalal, Rita P. ;
Shah, Sukrut ;
Wainberg, Zev A. ;
Chung, Hyun Cheol .
GASTRIC CANCER, 2019, 22 (04) :828-837
[4]   Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].
Borghaei, H. ;
Paz-Ares, L. ;
Horn, L. ;
Spigel, D. R. ;
Steins, M. ;
Ready, N. E. ;
Chow, L. Q. ;
Vokes, E. E. ;
Felip, E. ;
Holgado, E. ;
Barlesi, F. ;
Kohlhaeufl, M. ;
Arrieta, O. ;
Burgio, M. A. ;
Fayette, J. ;
Lena, H. ;
Poddubskaya, E. ;
Gerber, D. E. ;
Gettinger, S. N. ;
Rudin, C. M. ;
Rizvi, N. ;
Crino, L. ;
Blumenschein, G. R. ;
Antonia, S. J. ;
Dorange, C. ;
Harbison, C. T. ;
Finckenstein, F. Graf ;
Brahmer, J. R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639
[5]   Neoantigen-specific stem cell memory-like CD4+ T cells mediate CD8+ T cell-dependent immunotherapy of MHC class II-negative solid tumors [J].
Brightman, Spencer E. E. ;
Becker, Angelica ;
Thota, Rukman R. R. ;
Naradikian, Martin S. S. ;
Chihab, Leila ;
Zavala, Karla Soria ;
Griswold, Ryan Q. Q. ;
Dolina, Joseph S. S. ;
Cohen, Ezra E. W. ;
Miller, Aaron M. M. ;
Peters, Bjoern ;
Schoenberger, Stephen P. P. .
NATURE IMMUNOLOGY, 2023, 24 (8) :1345-1357
[6]   Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression [J].
Chen, Limo ;
Gibbons, Don L. ;
Goswami, Sangeeta ;
Cortez, Maria Angelica ;
Ahn, Young-Ho ;
Byers, Lauren A. ;
Zhang, Xuejun ;
Yi, Xiaohui ;
Dwyer, David ;
Lin, Wei ;
Diao, Lixia ;
Wang, Jing ;
Roybal, Jonathon D. ;
Patel, Mayuri ;
Ungewiss, Christin ;
Peng, David ;
Antonia, Scott ;
Mediavilla-Varela, Melanie ;
Robertson, Gordon ;
Jones, Steve ;
Suraokar, Milind ;
Welsh, James W. ;
Erez, Baruch ;
Wistuba, Ignacio I. ;
Chen, Lieping ;
Peng, Di ;
Wang, Shanshan ;
Ullrich, Stephen E. ;
Heymach, John V. ;
Kurie, Jonathan M. ;
Qin, F. Xiao-Feng .
NATURE COMMUNICATIONS, 2014, 5
[7]   Gastric Cancer Epidemiology and Risk Factors [J].
de Martel, Catherine ;
Forman, David ;
Plummer, Martyn .
GASTROENTEROLOGY CLINICS OF NORTH AMERICA, 2013, 42 (02) :219-+
[8]   Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic Triple-Negative Breast Cancer A Phase 1 Study [J].
Emens, Leisha A. ;
Cruz, Cristina ;
Eder, Joseph Paul ;
Braiteh, Fadi ;
Chung, Cathie ;
Tolaney, Sara M. ;
Kuter, Irene ;
Nanda, Rita ;
Cassier, Philippe A. ;
Delord, Jean-Pierre ;
Gordon, Michael S. ;
ElGabry, Ehab ;
Chang, Ching-Wei ;
Sarkar, Indrani ;
Grossman, William ;
O'Hear, Carol ;
Fasso, Marcella ;
Molinero, Luciana ;
Schmid, Peter .
JAMA ONCOLOGY, 2019, 5 (01) :74-82
[9]   Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial [J].
Fuchs, Charles S. ;
Ozguroglu, Mustafa ;
Bang, Yung-Jue ;
Di Bartolomeo, Maria ;
Mandala, Mario ;
Ryu, Min-Hee ;
Fornaro, Lorenzo ;
Olesinski, Tomasz ;
Caglevic, Christian ;
Chung, Hyun C. ;
Muro, Kei ;
Van Cutsem, Eric ;
Elme, Anneli ;
Thuss-Patience, Peter ;
Chau, Ian ;
Ohtsu, Atsushi ;
Bhagia, Pooja ;
Wang, Anran ;
Shih, Chie-Schin ;
Shitara, Kohei .
GASTRIC CANCER, 2022, 25 (01) :197-206
[10]   Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer [J].
Garcia-Martinez, Elena ;
Luengo Gil, Gines ;
Chaves Benito, Asuncion ;
Gonzalez-Billalabeitia, Enrique ;
Vicente Conesa, Mara Angeles ;
Garcia Garcia, Teresa ;
Garcia-Garre, Elisa ;
Vicente, Vicente ;
Ayala de la Pena, Francisco .
BREAST CANCER RESEARCH, 2014, 16 (06)