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Review | Open Access

Potential new applications of immunotherapy for neuroendocrine neoplasms: immune landscape, current status and future perspectives

Rilan Bai, Wenqian Li, Jiuwei Cui ( )
Cancer Center, the First Hospital of Jilin University, Changchun 130021, China
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Abstract

Neuroendocrine neoplasms (NENs) are a highly heterogeneous class of tumors arising from neuroendocrine cells and peptidergic neurons. After failure of first-line treatment, patients have poor prognosis and limited treatment options. Immune checkpoint inhibitors (ICIs) may be a powerful means of increasing therapeutic efficacy for such patients, but ICIs alone have low response rates and short disease control durations in most NENs and may be effective for only a portion of the population. ICIs combined with other immunotherapies, targeted therapies, or cytotoxic drugs have achieved some efficacy in patients with NENs and are worthy of further exploration to assess their benefits to the population. In addition, accumulating experimental and clinical evidence supports that the interaction between neuroendocrine and immune systems is essential to maintain homeostasis, and assessment of this broad neuroendocrine-immune correlation is essential for NEN treatment. In this review, we summarize the immune microenvironment characteristics, advances in immunotherapy, predictive biomarkers of ICI efficacy for NENs, and the effects of common endocrine hormones on the immune system, highlighting possible new application areas for this promising treatment in neglected NENs.

Keywords

immunotherapyhormonesNeuroendocrine neoplasmspredictive biomarker

References

1

Kulke MH, Shah MH, Benson AB, 3rd, Bergsland E, Berlin JD, Blaszkowsky LS, et al. Neuroendocrine tumors, version 1. 2015. J Natl Compr Canc Netw. 2015; 13: 78-108.
Crossref Google Scholar
2

Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008; 26: 3063-72.
Crossref Google Scholar
3

Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the incidence, prevalence, and survival outcomess in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017; 3: 1335-42.
Crossref Google Scholar
4

Lloyd RV, Osamura RY, Klöppel G, Rosai J. Who classification of tumours of endocrine organs. 4th ed. Geneva S: WHO. 2017.
5

Brighi N, Lamberti G, Manuzzi L, Maggio I, Campana D. Therapeutic options in lung neuroendocrine tumors: between established concepts and new hopes. Anticancer Drugs. 2019; 30: e0784.
Crossref Google Scholar
6

Kaderli RM, Spanjol M, Kollár A, Bütikofer L, Gloy V, Dumont RA, et al. Therapeutic options for neuroendocrine tumors: a systematic review and network meta-analysis. JAMA Oncol. 2019; 5: 480-9.
Crossref Google Scholar
7

Pavel M, O'toole D, Costa F, Capdevila J, Gross D, Kianmanesh R, et al. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 2016; 103: 172-85.
Crossref Google Scholar
8

Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013; 24: 152-60.
Crossref Google Scholar
9

Garcia-Carbonero R, Sorbye H, Baudin E, Raymond E, Wiedenmann B, Niederle B, et al. ENETS consensus guidelines for high-grade gastroenteropancreatic neuroendocrine tumors and neuroendocrine carcinomas. Neuroendocrinology. 2016; 103: 186-94.
Crossref Google Scholar
10

Vaddepally RK, Kharel P, Pandey R, Garje R, Chandra AB. Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers (Basel). 2020; 12: 738.
Crossref Google Scholar
11

Yoo C, Oh CR, Kim ST, Bae WK, Choi HJ, Oh DY, et al. Systemic treatment of advanced gastroenteropancreatic neuroendocrine tumors in Korea: literature review and expert opinion. Cancer Res Treat. 2021; 53: 291-300.
Crossref Google Scholar
12

Hellmann M, Ott PA, Zugazagoitia J, Ready NE, Spigel DR. Nivolumab (nivo) ± ipilimumab (ipi) in advanced small-cell lung cancer (SCLC): first report of a randomized expansion cohort from CheckMate 032. J Clin Oncol. 2017; 35(suppl 15): 8503.
Crossref Google Scholar
13

Chung HC, Lopez-Martin JA, Kao SC-H, Miller WH, Ros W, Gao B, et al. Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KEYNOTE-158. J Clin Oncol. 2018; 36: 8506.
Crossref Google Scholar
14

Nghiem P, Bhatia S, Daud A, Friedlander P, Kluger H, Kohrt H, et al. 22LBA Activity of PD-1 blockade with pembrolizumab as first systemic therapy in patients with advanced Merkel cell carcinoma. Eur J Cancer 2015; 51: S720-1.
Crossref Google Scholar
15

Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018; 379: 2220-9.
Crossref Google Scholar
16

Vijayvergia N, Dasari A, Deng M, Litwin S, Al-Toubah T, Alpaugh RK, et al. Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials. Br J Cancer. 2020; 122: 1309-14.
Crossref Google Scholar
17

Takahashi D, Kojima M, Suzuki T, Sugimoto M, Kobayashi S, Takahashi S, et al. Profiling the tumour immune microenvironment in pancreatic neuroendocrine neoplasms with multispectral imaging indicates distinct subpopulation characteristics concordant with WHO 2017 classification. Sci Rep. 2018; 8: 13166.
Crossref Google Scholar
18

De Hosson LD, Takkenkamp TJ, Kats-Ugurlu G, Bouma G, Bulthuis M, De Vries EGE, et al. Neuroendocrine tumours and their microenvironment. Cancer Immunol Immunother. 2020; 69: 1449-59.
Crossref Google Scholar
19

Cives M, Pelle E, Quaresmini D, Rizzo FM, Tucci M, Silvestris F. The tumor microenvironment in neuroendocrine tumors: biology and therapeutic implications. Neuroendocrinology. 2019; 109: 83-99.
Crossref Google Scholar
20

Milione M, Miceli R, Barretta F, Pellegrinelli A, Spaggiari P, Tagliabue G, et al. Microenvironment and tumor inflammatory features improve prognostic prediction in gastro-entero-pancreatic neuroendocrine neoplasms. J Pathol Clin Res. 2019; 5: 217-26.
Crossref Google Scholar
21

Lamarca A, Nonaka D, Breitwieser W, Ashton G, Barriuso J, Mcnamara MG, et al. PD-L1 expression and presence of TILs in small intestinal neuroendocrine tumours. Oncotarget. 2018; 9: 14922-38.
Crossref Google Scholar
22

Sampedro-Núñez M, Serrano-Somavilla A, Adrados M, CameselleTeijeiro JM, Blanco-Carrera C, Cabezas-Agricola JM, et al. Analysis of expression of the PD-1/PD-L1 immune checkpoint system and its prognostic impact in gastroenteropancreatic neuroendocrine tumors. Sci Rep. 2018; 8: 17812.
Crossref Google Scholar
23

Cavalcanti E, Armentano R, Valentini AM, Chieppa M, Caruso ML. Role of PD-L1 expression as a biomarker for GEP neuroendocrine neoplasm grading. Cell Death Dis. 2017; 8: e3004.
Crossref Google Scholar
24

Oktay E, Yalcin GD, Ekmekci S, Kahraman DS, Yalcin A, Degirmenci M, et al. Programmed cell death ligand-1 expression in gastroenteropancreatic neuroendocrine tumors. J Buon. 2019; 24: 779-90.
Google Scholar
25

Yang MW, Fu XL, Jiang YS, Chen XJ, Tao LY, Yang JY, et al. Clinical significance of programmed death 1/programmed death ligand 1 pathway in gastric neuroendocrine carcinomas. World J Gastroenterol. 2019; 25: 1684-96.
Crossref Google Scholar
26

Bösch F, Brüwer K, Altendorf-Hofmann A, Auernhammer CJ, Spitzweg C, Westphalen CB, et al. Immune checkpoint markers in gastroenteropancreatic neuroendocrine neoplasia. Endocr Relat Cancer. 2019; 26: 293-301.
Crossref Google Scholar
27

Pinato DJ, Vallipuram A, Evans JS, Wong C, Zhang H, Brown M, et al. Programmed cell death ligand expression drives immune tolerogenesis across the diverse subtypes of neuroendocrine tumours. Neuroendocrinology. 2021; 111: 465-74.
Crossref Google Scholar
28

Ali AS, Langer SW, Federspiel B, Hjortland GO, Janson ET. PD-L1 expression in gastroenteropancreatic neuroendocrine neoplasms grade 3. PLoS One. 2020; 15: e0243900.
Crossref Google Scholar
29

Van Riet J, Van De Werken HJG, Cuppen E, Eskens F, Tesselaar M, Van Veenendaal LM, et al. The genomic landscape of 85 advanced neuroendocrine neoplasms reveals subtype-heterogeneity and potential therapeutic targets. Nat Commun. 2021; 12: 4612.
Crossref Google Scholar
30

Scarpa A, Chang DK, Nones K, Corbo V, Patch AM, Bailey P, et al. Whole-genome landscape of pancreatic neuroendocrine tumours. Nature. 2017; 543: 65-71.
Crossref Google Scholar
31

Venizelos A, Elvebakken H, Perren A, Nikolaienko O, Deng W, Lothe IMB, et al. The molecular characteristics of high-grade gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer. 2021; 29: 1-14.
Crossref Google Scholar
32
Chi Y, Liu W, Zuo L, Wang Y, Zhao H. Abstract 4743: Genetic characteristics of PanNETs, Rectal NETs, Thoracic NETs and its correlation with efficacy of chemotherapy. Proceedings: AACR Annual Meeting 2020; April 27-28,2020 and June 22-24,2020; Philadelphia, PA, 2020.
33

Sabari JK, Julian RA, Ni A, Halpenny D, Hellmann MD, Drilon AE, et al. Outcomes of advanced pulmonary large cell neuroendocrine carcinoma stratified by RB1 loss, SLFN11 expression, and tumor mutational burden. J Clin Oncol. 2018; 36(suppl 15): e20568-e68.
Crossref Google Scholar
34

Da Silva A, Bowden M, Zhang S, Masugi Y, Thorner AR, Herbert ZT, et al. Characterization of the neuroendocrine tumor immune microenvironment. Pancreas. 2018; 47: 1123-9.
Crossref Google Scholar
35

Webster JI, Tonelli L, Sternberg EM. Neuroendocrine regulation of immunity. Annu Rev Immunol. 2002; 20: 125-63.
Crossref Google Scholar
36

Klein JR. Dynamic interactions between the immune system and the neuroendocrine system in health and disease. Front Endocrinol (Lausanne). 2021; 12: 655982.
Crossref Google Scholar
37

Johnson EW, Hughes TK, Jr., Smith EM. ACTH enhancement of T-lymphocyte cytotoxic responses. Cell Mol Neurobiol. 2005; 25: 743-57.
Crossref Google Scholar
38

Wira CR, Rodriguez-Garcia M, Patel MV. The role of sex hormones in immune protection of the female reproductive tract. Nat Rev Immunol. 2015; 15: 217-30.
Crossref Google Scholar
39

Walker SE. Estrogen and autoimmune disease. Clin Rev Allergy Immunol. 2011; 40: 60-5.
Crossref Google Scholar
40

Gubbels Bupp MR, Potluri T, Fink AL, Klein SL. The confluence of sex hormones and aging on immunity. Front immunol. 2018; 9: 1269.
Crossref Google Scholar
41

Kissick HT, Sanda MG, Dunn LK, Pellegrini KL, On ST, Noel JK, et al. Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proc Natl Acad Sci U S A. 2014; 111: 9887-92.
Crossref Google Scholar
42

Gubbels Bupp MR, Jorgensen TN. Androgen-induced immunosuppression. Front Immunol. 2018; 9: 794.
Crossref Google Scholar
43

Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017; 127: 2930-40.
Crossref Google Scholar
44

Prat A, Navarro A, Paré L, Reguart N, Galván P, Pascual T, et al. Immune-related gene expression profiling after PD-1 blockade in non-small cell lung carcinoma, head and neck squamous cell carcinoma, and melanoma. Cancer Res. 2017; 77: 3540-50.
Crossref Google Scholar
45

Benten W P, Lieberherr M, Giese G, Wrehlke C, Stamm O, Sekeris CE, et al. Functional testosterone receptors in plasma membranes of T cells. FASEB J. 1999; 13: 123-33.
Crossref Google Scholar
46

Guan X, Polesso F, Wang C, Sehrawat A, Hawkins RM, Murray SE, et al. Androgen receptor activity in T cells limits checkpoint blockade efficacy. Nature. 2022; 606: 791-6.
Crossref Google Scholar
47

Bernard V, Young J, Binart N. Prolactin - a pleiotropic factor in health and disease. Nat Rev Endocrinol. 2019; 15: 356-65.
Crossref Google Scholar
48

Borba VV, Zandman-Goddard G, Shoenfeld Y. Prolactin and autoimmunity: the hormone as an inflammatory cytokine. Best Pract Res Clin Endocrinol Metab. 2019; 33: 101324.
Crossref Google Scholar
49

Weigent DA. Lymphocyte GH-axis hormones in immunity. Cell Immunol. 2013; 285: 118-32.
Crossref Google Scholar
50

Mehnert JM, Bergsland E, O'neil BH, Santoro A, Schellens JHM, Cohen RB, et al. Pembrolizumab for the treatment of programmed death-ligand 1-positive advanced carcinoid or pancreatic neuroendocrine tumors: results from the KEYNOTE-028 study. Cancer. 2020; 126: 3021-30.
Crossref Google Scholar
51

Strosberg J, Mizuno N, DoiT, Grande E, Delord JP, ShapiraFrommer R, et al. Efficacy and safety of pembrolizumab in previously treated advanced neuroendocrine tumors: results from the phase Ⅱ KEYNOTE-158 study. Clin Cancer Res. 2020; 26: 2124-30.
Crossref Google Scholar
52

Yao JC, Strosberg J, Fazio N, Pavel ME, Bergsland E, Ruszniewski P, et al. Spartalizumab in metastatic, well/poorly-differentiated neuroendocrine neoplasms. Endocr Relat Cancer. 2021; 28: 161-72.
Crossref Google Scholar
53

Patel SP, Othus M, Chae YK, Giles FJ, Hansel DE, Singh PP, et al. A phase Ⅱ basket trial of dual Anti-CTLA-4 and Anti-PD-1 blockade in rare tumors (DART SWOG 1609) in patients with nonpancreatic neuroendocrine tumors. Clin Cancer Res. 2020; 26: 2290-6.
Crossref Google Scholar
54

Lu M, Zhang P, Zhang Y, Li Z, Gong J, Li J, et al. Efficacy, safety, and biomarkers of toripalimab in patients with recurrent or metastatic neuroendocrine neoplasms: a multiple-center phase Ib trial. Clin Cancer Res. 2020; 26: 2337-45.
Crossref Google Scholar
55

Riesco Martínez MC, Capdevilla J, Alonso V, Jimenez-Fonseca P, Teulè A, Grande E, et al. Nivolumab plus platinum doublet chemotherapy as first line therapy in unresectable, locally advanced or metastatic G3 neuroendocrine neoplasms (NENs) of the gastroenteropancreatic (GEP) tract or unknown (UK) origin: preliminary results from the phase Ⅱ NICE-NEC trial. Ann Oncol. 2021; 32(suppl 5): S908-9.
Crossref Google Scholar
56

Bongiovanni A, Maiorano BA, Azzali I, Liverani C, Bocchini M, Fausti V, et al. Activity and safety of immune checkpoint inhibitors in neuroendocrine neoplasms: a systematic review and metaanalysis. pharmaceuticals (Basel). 2021; 14: 476.
Crossref Google Scholar
57

Park EJ, Park HJ, Kim KW, Suh CH, Yoo C, Chae YK, et al. Efficacy of immune checkpoint inhibitors against advanced or metastatic neuroendocrine neoplasms: a systematic review and meta-analysis. Cancers (Basel). 2022; 14: 794.
Crossref Google Scholar
58

Chan JA, Raj NP, Aggarwal RR, Calabrese S, Demore A, Dhawan MS, et al. Phase Ⅱ study of pembrolizumab-based therapy in previously treated extrapulmonary poorly differentiated neuroendocrine carcinomas: results of Part B (pembrolizumab + chemotherapy). J Clin Oncol. 2021; 39(suppl 15): 4148-48.
Crossref Google Scholar
59

Fang L, Arvind D, Dowlati A, Mohamed A. Role of immunotherapy in gastro-enteropancreatic neuroendocrine neoplasms (GEPNENs): current advances and future directions. J Neuroendocr. 2021; 33: E12943.
Crossref Google Scholar
60

Ott PA, Bang YJ, Piha-Paul SA, Razak ARA, Bennouna J, Soria JC, et al. T-cell-inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028. J Clin Oncol. 2019; 37: 318-27.
Crossref Google Scholar
61

Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, et al. Durable tumor regression and overall survival in patients with advanced merkel cell carcinoma receiving pembrolizumab as first-line therapy. J Clin Oncol. 2019; 37: 693-702.
Crossref Google Scholar
62

Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'angelo SP, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016; 17: 1374-85.
Crossref Google Scholar
63
Abstracts presented at the 13th Annual multidisciplinary neuroendocrine tumor medical virtual symposium of the North American Neuroendocrine Tumor Society, October 2-3,2020. Pancreas. 2021; 50: 441-67.
Crossref
64

Fottner CAL, Ferrata M, Krug S, Michl P, Schad A, Roth W, et al. A Phase Ⅱ, open label, multicenter trial of Avelumab in patients with advanced, metastatic highgrade neuroendocrine carcinomas NEC G3 (WHO 2010) progressive after first-line chemotherapy (AVENEC). J Clin Oncol. 2019; 37: 4103.
Crossref Google Scholar
65

Gile JJ, Liu AJ, Mcgarrah PW, Eiring RA, Hobday TJ, Starr JS, et al. Efficacy of checkpoint inhibitors in neuroendocrine neoplasms: mayo clinic experience. Pancreas. 2021; 50: 500-5.
Crossref Google Scholar
66

Kelly K, Infante JR, Taylor MH, Patel MR, Wong DJ, Iannotti N, et al. Safety profile of avelumab in patients with advanced solid tumors: a pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. Cancer. 2018; 124: 2010-7.
Crossref Google Scholar
67

D'angelo SP, Russell J, Lebbé C, Chmielowski B, Gambichler T, Grob JJ, et al. Efficacy and safety of first-line avelumab treatment in patients with stage IV metastatic Merkel cell carcinoma: a preplanned interim analysis of a clinical trial. JAMA Oncol. 2018; 4: e180077.
Crossref Google Scholar
68

Walker JW, Lebbé C, Grignani G, Nathan P, Dirix L, Fenig E, et al. Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program. J Immunother Cancer. 2020; 8: e000313.
Crossref Google Scholar
69

Topalian SL, Bhatia S, Hollebecque A, Awada A, Boer JPD, Kudchadkar RR, et al. Abstract Ct074: Non-comparative, openlabel, multiple cohort, phase 1/2 study to evaluate nivolumab (NIVO) in patients with virus-associated tumors (Checkmate 358): efficacy and safety in Merkel cell carcinoma (MCC). Cancer Res. 2017; 77(13 suppl): Ct074.
Crossref Google Scholar
70

Yao JC, Strosberg J, Fazio N, Pavel ME, Ruszniewski P, Bergsland E, et al. Activity & safety of spartalizumab (PDR001) in patients (Pts), with advanced Neuroendocrine Tumors (NET) of Pancreatic (Pan) Gastrointestinal (GI), or Thoracic (T) Origin, & Gastroenteropancreatic Neuroendocrine Carcinoma (GEP NEC) who have progressed on prior treatment (Tx). Ann Oncol. 2018; 29(suppl 8): Viii467-78.
Crossref Google Scholar
71

Owen DH, Wei L, Goyal A, Zhou Y, Suffren S-A, Jacob R, et al. CLO20-054: a phase 2 trial of nivolumab and temozolomide in advanced neuroendocrine tumors (NETs): interim efficacy analysis. J Natl Compr Canc Netw. 2020; 18. DOI: 10.6004/jnccn.2019.7460.
Crossref Google Scholar
72

Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018; 378: 2078-92.
Crossref Google Scholar
73

Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, et al. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensivestage small-cell lung cancer. J Clin Oncol. 2016; 34: 3740-8.
Crossref Google Scholar
74

Schultheis AM, Scheel AH, Ozretić L, George J, Thomas RK, Hagemann T, et al. PD-L1 expression in small cell neuroendocrine carcinomas. Eur J Cancer. 2015; 51: 421-6.
Crossref Google Scholar
75

Kim YJ, Keam B, Ock CY, Song S, Kim M, Kim SH, et al. A phase Ⅱ study of pembrolizumab and paclitaxel in patients with relapsed or refractory small-cell lung cancer. Lung Cancer. 2019; 136: 122-8.
Crossref Google Scholar
76

Yi M, Jiao D, Qin S, Chu Q, Wu K, Li A. Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment. Mol Cancer. 2019; 18: 60.
Crossref Google Scholar
77

Halperin DM, Liu S, Dasari A, Fogelman DR, Yao JC. A phase Ⅱ trial of atezolizumab and bevacizumab in patients with advanced, progressive neuroendocrine tumors (NETs). J Clin Oncol. 2020; 38(suppl 4): 619.
Crossref Google Scholar
78

Baranwal VK, Negi N, Khurana P. Comparative transcriptomics of leaves of five mulberry accessions and cataloguing structural and expression variants for future prospects. PLoS One. 2021; 16: e0252246.
Crossref Google Scholar
79

Shen L, Yu X, Lu M, Zhang X, Su W. Surufatinib in combination with toripalimab in patients with advanced neuroendocrine carcinoma: results from a multicenter, open-label, single-arm, phase Ⅱ trial. J Clin Oncol. 2021; 39(suppl 15): e16199-e99.
Crossref Google Scholar
80

Klein O, Kee D, Markman B, Michael M, Underhill C, Carlino MS, et al. Immunotherapy of ipilimumab and nivolumab in patients with advanced neuroendocrine tumors: a subgroup analysis of the CA209- 538 clinical trial for rare cancers. Clin Cancer Res. 2020; 26: 4454-9.
Crossref Google Scholar
81

Owonikoko TK, Kim H, Govindan R, Ready N, Reck M, Peters S, et al. Nivolumab (Nivo) plus ipilimumab (Ipi), nivo, or placebo (Pbo) as maintenance therapy in patients (Pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (Chemo): results from the double-blind, randomized phase Ⅲ checkmate 451 study. Ann Oncol. 2019; 30: Ⅱ77.
Crossref Google Scholar
82

Capdevila J, Teule A, López C, García-Carbonero R, Benavent M, Custodio A, et al. 1157O - A multi-cohort phase Ⅱ study of durvalumab plus tremelimumab for the treatment of patients (pts) with advanced neuroendocrine neoplasms (NENs) of gastroenteropancreatic or lung origin: The DUNE trial (GETNE 1601). Ann Oncol. 2020; 31(suppl 4): S711-24.
Crossref Google Scholar
83

Uboha NV, Milhem MM, Kovacs C, Amin A, Magley A, Purkayastha DD, et al. Phase II study of spartalizumab (PDR001) and LAG525 in advanced solid tumors and hematologic malignancies. JCO. 2019; 37(suppl 15): 2553.
Crossref Google Scholar
84

Kim C, Liu SV, Subramaniam DS, Torres T, Loda M, Esposito G, et al. Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung. J Immunother Cancer. 2020; 8: e000980.
Crossref Google Scholar
85

Long GV, Dummer R, Hamid O, Gajewski T, Caglevic C, Dalle S, et al. Epacadostat (E) plus pembrolizumab (P) versus pembrolizumab alone in patients (pts) with unresectable or metastatic melanoma: Results of the phase 3 ECHO-301/ KEYNOTE-252 study. J Clin Oncol. 2018; 36(suppl 15): 108.
Crossref Google Scholar
86

Advani R, Flinn I, Popplewell L, Forero A, Bartlett NL, Ghosh N, et al. CD47 blockade by Hu5F9-G4 and rituximab in nonhodgkin's lymphoma. N Engl J Med. 2018; 379: 1711-21.
Crossref Google Scholar
87

Zhang N, Hao X. Epigenetic modulation of the tumor immune microenvironment by nanoinducers to potentiate cancer immunotherapy. Cancer Biol Med. 2021; 19: 1-3.
Crossref Google Scholar
88

Kiyotani K, Toyoshima Y, Nakamura Y. Personalized immunotherapy in cancer precision medicine. Cancer Biol Med. 2021; 18: 955-65.
Crossref Google Scholar
89

Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017; 390: 1853-62.
Crossref Google Scholar
90

Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous nonsmall-cell lung cancer. N Engl J Med. 2015; 373: 1627-39.
Crossref Google Scholar
91

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus Chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016; 375: 1823-33.
Crossref Google Scholar
92

Shah MH, Goldner WS, Benson AB, Bergsland E, Blaszkowsky LS, Brock P, et al. Neuroendocrine and adrenal tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021; 19: 839-68.
Crossref Google Scholar
93

Wang VE, Urisman A, Albacker L, Ali S, Miller V, Aggarwal R, et al. Checkpoint inhibitor is active against large cell neuroendocrine carcinoma with high tumor mutation burden. J Immunother Cancer. 2017; 5: 75.
Crossref Google Scholar
94

Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019; 51: 202-6.
Crossref Google Scholar
95

Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020; 21: 1353-65.
Crossref Google Scholar
96

Necchi A, Raggi D, Gallina A, Ross JS, Farè E, Giannatempo P, et al. Impact of molecular subtyping and immune infiltration on pathological response and outcome following neoadjuvant pembrolizumab in muscle-invasive bladder cancer. Eur Urol. 2020; 77: 701-10.
Crossref Google Scholar
97

Masuda K, Banno K, Yanokura M, Kobayashi Y, Kisu I, Ueki A, et al. Relationship between DNA mismatch repair deficiency and endometrial cancer. Mol Biol Int. 2011; 2011: 256063.
Crossref Google Scholar
98

Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015; 372: 2509-20.
Crossref Google Scholar
99

Kidd M, Eick G, Shapiro MD, Camp RL, Mane SM, Modlin IM. Microsatellite instability and gene mutations in transforming growth factor-beta type Ⅱ receptor are absent in small bowel carcinoid tumors. Cancer. 2005; 103: 229-36.
Crossref Google Scholar
100

Arnason T, Sapp HL, Rayson D, Barnes PJ, Drewniak M, Nassar BA, et al. Loss of expression of DNA mismatch repair proteins is rare in pancreatic and small intestinal neuroendocrine tumors. Arch Pathol Lab Med. 2011; 135: 1539-44.
Crossref Google Scholar
101

Sahnane N, Furlan D, Monti M, Romualdi C, Vanoli A, Vicari E, et al. Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathologic entity. Endocr Relat Cancer. 2015; 22: 35-45.
Crossref Google Scholar
102

Katz SC, Donkor C, Glasgow K, Pillarisetty VG, Gönen M, Espat NJ, et al. T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases. HPB (Oxford). 2010; 12: 674-83.
Crossref Google Scholar
103

Giannetta E, La Salvia A, Rizza L, Muscogiuri G, Campione S, Pozza C, et al. Are markers of systemic inflammatory response useful in the management of patients with neuroendocrine neoplasms? Front Endocrinol (Lausanne). 2021; 12: 672499.
Crossref Google Scholar
Cancer Biology & Medicine
Volume 19 Issue 12,
December 2022
Pages 1649-1661
DOI: 10.20892/j.issn.2095-3941.2022.0489
Cite this article:
Bai R, Li W, Cui J. Potential new applications of immunotherapy for neuroendocrine neoplasms: immune landscape, current status and future perspectives. Cancer Biology & Medicine, 2022, 19(12): 1649-1661. https://doi.org/10.20892/j.issn.2095-3941.2022.0489

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Received: 12 August 2022
Accepted: 19 September 2022
Published: 12 December 2022
©2022 Cancer Biology & Medicine.

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