REFERENCES
1. Kallen ME, Hornick JL. The 2020 WHO Classification: what’s new in soft tissue tumor pathology? Am J Surg Pathol 2021;45:e1-e23.
2. Verschoor AJ, Litière S, Marréaud S, et al. Survival of soft tissue sarcoma patients after completing six cycles of first-line anthracycline containing treatment: an EORTC-STBSG database study. Clin Sarcoma Res 2020;10:18.
3. Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res 1991;(262):3-11.
4. Wilky BA, Trucco MM, Subhawong TK, et al. Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Lancet Oncol 2019;20:837-48.
5. Florou V, Rosenberg AE, Wieder E, et al. Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution. J Immunother Cancer 2019;7:213.
6. Wagner MJ, Othus M, Patel SP, et al. Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART). J Immunother Cancer 2021;9:e002990.
7. D’Angelo SP, Mahoney MR, Van Tine BA, et al. A multi-center phase II study of nivolumab +/- ipilimumab for patients with metastatic sarcoma (Alliance A091401). J Clin Oncol 2017;35:11007.
8. D’Angelo SP, Melchiori L, Merchant MS, et al. Antitumor activity associated with prolonged persistence of adoptively transferred NY-ESO-1 c259T cells in synovial sarcoma. Cancer Discov 2018;8:944-57.
9. Tawbi HA, Burgess M, Bolejack V, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 2017;18:1493-501.
10. Naqash AR, O’Sullivan Coyne GH, Moore N, et al. Phase II study of atezolizumab in advanced alveolar soft part sarcoma (ASPS). J Clin Oncol 2021;39:11519.
11. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity 2013;39:1-10.
12. Galluzzi L, Vitale I, Warren S, et al. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J Immunother Cancer 2020;8:e000337.
13. Dufresne A, Lesluyes T, Ménétrier-Caux C, et al. Specific immune landscapes and immune checkpoint expressions in histotypes and molecular subtypes of sarcoma. Oncoimmunology 2020;9:1792036.
14. Chávez-Galán L, Olleros ML, Vesin D, Garcia I. Much More than M1 and M2 macrophages, there are also CD169(+) and TCR(+) macrophages. Front Immunol 2015;6:263.
15. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015;15:486-99.
16. Spranger S, Sivan A, Corrales L, Gajewski TF. Tumor and host factors controlling antitumor immunity and efficacy of cancer immunotherapy. Adv Immunol 2016;130:75-93.
17. Wisdom AJ, Mowery YM, Hong CS, et al. Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy. Nat Commun 2020;11:6410.
18. Hildebrand KM, Singla AK, McNeil R, et al. The KrasG12D;Trp53fl/fl murine model of undifferentiated pleomorphic sarcoma is macrophage dense, lymphocyte poor, and resistant to immune checkpoint blockade. PLoS One 2021;16:e0253864.
19. Gutierrez WR, Scherer A, McGivney GR, et al. Divergent immune landscapes of primary and syngeneic Kras-driven mouse tumor models. Sci Rep 2021;11:1098.
20. Petitprez F, de Reyniès A, Keung EZ, et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature 2020;577:556-60.
21. Hu C, Chen B, Huang Z, et al. Comprehensive profiling of immune-related genes in soft tissue sarcoma patients. J Transl Med 2020;18:337.
22. Riaz N, Morris L, Havel JJ, Makarov V, Desrichard A, Chan TA. The role of neoantigens in response to immune checkpoint blockade. Int Immunol 2016;28:411-9.
23. Goodman AM, Kato S, Bazhenova L, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther 2017;16:2598-608.
24. Chalmers ZR, Connelly CF, Fabrizio D, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 2017;9:34.
25. Groisberg R, Roszik J, Conley AP, et al. Genomics, morphoproteomics, and treatment patterns of patients with alveolar soft part sarcoma and response to multiple experimental therapies. Mol Cancer Ther 2020;19:1165-72.
26. Painter CA, Jain E, Tomson BN, et al. The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research. Nat Med 2020;26:181-7.
27. Mc Granahan N, Furness AJS, Rosenthal R, et al. Clonal neoantigens elict T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 2016;351:1463-9.
28. Rizvi NA, Hellmann MD, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2016;348:124-8.
29. Chae YK, Viveiros P, Lopes G, et al. Clinical and immunological implications of frameshift mutations in lung cancer. J Thorac Oncol 2019;14:1807-17.
30. George S, Miao D, Demetri GD, et al. Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity 2017;46:197-204.
31. Kato S, Goodman A, Walavalkar V, Barkauskas DA, Sharabi A, Kurzrock R. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res 2017;23:4242-50.
32. Pollack SM, Redman MW, Baker KK, et al. Assessment of doxorubicin and pembrolizumab in patients with advanced anthracycline-naive sarcoma: a phase 1/2 nonrandomized clinical trial. JAMA Oncol 2020;6:1778-82.
33. DuBois S, Demetri G. Markers of angiogenesis and clinical features in patients with sarcoma. Cancer 2007;109:813-9.
34. Shurell E, Singh AS, Crompton JG, et al. Characterizing the immune microenvironment of malignant peripheral nerve sheath tumor by PD-L1 expression and presence of CD8+ tumor infiltrating lymphocytes. Oncotarget 2016;7:64300-8.
35. Hack SP, Zhu AX, Wang Y. Augmenting anticancer immunity through combined targeting of angiogenic and PD-1/PD-L1 pathways: challenges and opportunities. Front Immunol 2020;11:598877.
36. Martin-Broto J, Hindi N, Grignani G, et al. Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial. J Immunother Cancer 2020;8:e001561.
37. Xie L, Xu J, Sun X, et al. Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial. J Immunother Cancer 2020;8:e000798.
38. Zhang M, Zhang YY, Chen Y, Wang J, Wang Q, Lu H. TGF-β signaling and resistance to cancer therapy. Front Cell Dev Biol 2021;9:786728.
39. Verrecchia F, Rédini F. Transforming growth factor-β signaling plays a pivotal role in the interplay between osteosarcoma cells and their microenvironment. Front Oncol 2018;8:133.
40. Kim BG, Malek E, Choi SH, Ignatz-Hoover JJ, Driscoll JJ. Novel therapies emerging in oncology to target the TGF-β pathway. J Hematol Oncol 2021;14:55.
41. Ghisoli M, Barve M, Mennel R, et al. Three-year follow up of GMCSF/bi-shRNA(furin) DNA-transfected autologous tumor immunotherapy (Vigil) in metastatic advanced Ewing’s sarcoma. Mol Ther 2016;24:1478-83.
42. Läubli H, Pearce OM, Schwarz F, et al. Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer. Proc Natl Acad Sci U S A 2014;111:14211-6.
43. Lübbers J, Rodríguez E, van Kooyk Y. Modulation of immune tolerance via siglec-sialic acid interactions. Front Immunol 2018;9:2807.
44. de Wall S, Santegoets KCM, van Houtum EJH, Büll C, Adema GJ. Sialoglycans and siglecs can shape the tumor immune microenvironment. Trends Immunol 2020;41:274-85.
45. Sun J, Lu Q, Sanmamed MF, Wang J. Siglec-15 as an emerging target for next-generation cancer immunotherapy. Clin Cancer Res 2021;27:680-8.
46. Fan MK, Zhang GC, Chen W, et al. Siglec-15 promotes tumor progression in osteosarcoma via DUSP1/MAPK pathway. Front Oncol 2021;11:710689.
47. Li B, Zhang B, Wang X, et al. Expression signature, prognosis value, and immune characteristics of Siglec-15 identified by pan-cancer analysis. Oncoimmunology 2020;9:1807291.
48. Dobrenkov K, Ostrovnaya I, Gu J, Cheung IY, Cheung NK. Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults. Pediatr Blood Cancer 2016;63:1780-5.
49. Carvajal RD, Agulnik M, Ryan CW, et al. Trivalent ganglioside vaccine and immunologic adjuvant versus adjuvant alone in metastatic sarcoma patients rendered disease-free by surgery: a randomized phase 2 trial. J Clin Oncol 2014;32:10520.
50. Miwa S, Nishida H, Tanzawa Y, et al. Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma. Cancer 2017;123:1576-84.
51. Nowicki TS, Berent-Maoz B, Cheung-Lau G, et al. A pilot trial of the combination of transgenic NY-ESO-1-reactive adoptive cellular therapy with dendritic cell vaccination with or without ipilimumab. Clin Cancer Res 2019;25:2096-108.
52. D’angelo SP, Mahoney MR, Van Tine BA, et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol 2018;19:416-26.
53. Teng MW, Ngiow SF, Ribas A, Smyth MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res 2015;75:2139-45.
54. Dancsok AR, Setsu N, Gao D, et al. Expression of lymphocyte immunoregulatory biomarkers in bone and soft-tissue sarcomas. Mod Pathol 2019;32:1772-85.
55. van Erp AEM, Versleijen-Jonkers YMH, Hillebrandt-Roeffen MHS, et al. Expression and clinical association of programmed cell death-1, programmed death-ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent. Oncotarget 2017;8:71371-84.
56. Nafia I, Toulmonde M, Bortolotto D, et al. IDO targeting in sarcoma: biological and clinical implications. Front Immunol 2020;11:274.
57. Pollack SM, He Q, Yearley JH, et al. T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. Cancer 2017;123:3291-304.
58. D’Angelo SP, Shoushtari AN, Agaram NP, et al. Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment. Hum Pathol 2015;46:357-65.
59. Sorbye SW, Kilvaer T, Valkov A, et al. Prognostic impact of lymphocytes in soft tissue sarcomas. PLoS One 2011;6:e14611.
60. Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014;515:568-71.
61. Keung EZ, Burgess M, Salazar R, et al. Correlative analyses of the SARC028 trial reveal an association between sarcoma-associated immune infiltrate and response to pembrolizumab. Clin Cancer Res 2020;26:1258-66.
62. Helmink BA, Reddy SM, Gao J, et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature 2020;577:549-55.
63. Chen L, Oke T, Siegel N, et al. The immunosuppressive niche of soft-tissue sarcomas is sustained by tumor-associated macrophages and characterized by intratumoral tertiary lymphoid structures. Clin Cancer Res 2020;26:4018-30.
64. Italiano A, Bessede A, Bompas E, et al. PD1 inhibition in soft-tissue sarcomas with tertiary lymphoid structures: a multicenter phase II trial. J Clin Oncol 2021;39:11507.
65. Toulmonde M, Penel N, Adam J, et al. Use of PD-1 targeting, macrophage infiltration, and IDO pathway activation in sarcomas: a phase 2 clinical trial. JAMA Oncol 2018;4:93-7.
66. Meyer C, Cagnon L, Costa-Nunes CM, et al. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother 2014;63:247-57.
67. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 2009;58:49-59.
68. Highfill SL, Cui Y, Giles AJ, et al. Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci Transl Med 2014;6:237ra67.
70. Kakimoto T, Matsumine A, Kageyama S, et al. Immunohistochemical expression and clinicopathological assessment of the cancer testis antigens NY-ESO-1 and MAGE-A4 in high-grade soft-tissue sarcoma. Oncol Lett 2019;17:3937-43.
71. Iura K, Kohashi K, Ishii T, et al. MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1. Virchows Arch 2017;471:383-92.
72. Ramachandran I, Lowther DE, Dryer-Minnerly R, et al. Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma. J Immunother Cancer 2019;7:276.
73. Tabak SA, Khalifa SE, Fathy Y. HER-2 immunohistochemical expression in bone sarcomas: a new hope for osteosarcoma patients. Open Access Maced J Med Sci 2018;6:1555-60.
74. Xiao W, Wang J, Wen X, et al. Chimeric antigen receptor-modified T-cell therapy for platelet-derived growth factor receptor α-positive rhabdomyosarcoma. Cancer 2020;126 Suppl 9:2093-100.
75. D’Angelo SP, Conley AP, Kelly CM, et al. Pilot study of NKTR214 and nivolumab in patients with sarcomas. J Clin Oncol 2019;37(15_suppl):11010.
76. Zhang S, Kohli K, Black RG, et al. Systemic interferon-γ increases MHC class I expression and T-cell infiltration in cold tumors: results of a phase 0 clinical trial. Cancer Immunol Res 2019;7:1237-43.
77. Fabian KP, Wolfson B, Hodge JW. From immunogenic cell death to immunogenic modulation: select chemotherapy regimens induce a spectrum of immune-enhancing activities in the tumor microenvironment. Front Oncol 2021;11:728018.
78. Wang YJ, Fletcher R, Yu J, Zhang L. Immunogenic effects of chemotherapy-induced tumor cell death. Genes Dis 2018;5:194-203.
79. Pfirschke C, Engblom C, Rickelt S, et al. Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy. Immunity 2016;44:343-54.
80. Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 2013;39:74-88.
81. Mattarollo SR, Loi S, Duret H, Ma Y, Zitvogel L, Smyth MJ. Pivotal role of innate and adaptive immunity in anthracycline chemotherapy of established tumors. Cancer Res 2011;71:4809-20.
82. Ramakrishnan R, Assudani D, Nagaraj S, et al. Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice. J Clin Invest 2010;120:1111-24.
83. Sistigu A, Yamazaki T, Vacchelli E, et al. Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med 2014;20:1301-9.
84. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9:162-74.
85. Germano G, Frapolli R, Simone M, et al. Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res 2010;70:2235-44.
86. Ito K, Hamamichi S, Abe T, et al. Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models. Cancer Sci 2017;108:2273-80.
87. Livingston MB, Jagosky MH, Robinson MM, et al. Phase II study of pembrolizumab in combination with doxorubicin in metastatic and unresectable soft-tissue sarcoma. Clin Cancer Res 2021;27:6424-31.
88. Gordon EM, Chua-Alcala VS, Kim K, et al. SAINT: results of a phase 1/2 study of safety/efficacy using safe amounts of ipilimumab, nivolumab, and trabectedin as first-line treatment of advanced soft tissue sarcoma. J Clin Oncol 2019;37:11016.
89. Nathenson M, Choy E, Carr ND, et al. Phase II study of eribulin and pembrolizumab in patients (pts) with metastatic soft tissue sarcomas (STS): report of LMS cohort. J Clin Oncol 2020;38:11559.
90. Le Cesne A, Marec-Berard P, Blay JY, et al. Programmed cell death 1 (PD-1) targeting in patients with advanced osteosarcomas: results from the PEMBROSARC study. Eur J Cancer 2019;119:151-7.