Processes 2019, 7,37
14. Chaudhary, B.; Elkord, E. Regulatory T cells in the tumor microenvironment and cancer progression: Role
and therapeutic targeting. Vaccines 2016, 4, 28. [CrossRef]
15. Fleming, V.; Hu, X.; Weber, R.; Nagibin, V.; Groth, C.; Altevogt, P.; Utikal, J.; Umansky, V. Targeting
myeloid-derived suppressor cells to bypass tumor-induced immunosuppression. Front. Immunol. 2018, 9,
398. [CrossRef]
16. Beyer, M.; Schultze, J.L. Regulatory T cells in cancer. Blood 2006, 108, 804–811. [CrossRef][PubMed]
17. De Visser, K.E.; Eichten, A.; Coussens, L.M. Paradoxical roles of the immune system during cancer
development. Nat. Rev. Cancer 2006, 6, 24–37. [CrossRef][PubMed]
18. Palucka, A.K.; Coussens, L.M. The basis of oncoimmunology. Cell 2016, 164, 1233–1247. [CrossRef]
19. Blank, C.; Mackensen, A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: An update on
implications for chronic infections and tumor evasion. Cancer Immunol. Immunother. 2007, 56, 739–745.
[CrossRef]
20. Jiang, Y.; Li, Y.; Zhu, B. T-cell exhaustion in the tumor microenvironment. Cell Death Dis. 2015, 6, e1792.
[CrossRef]
21. Seifert, A.M.; Zeng, S.; Zhang, J.Q.; Kim, T.S.; Cohen, N.A.; Beckman, M.J.; Medina, B.D.; Maltbaek, J.H.;
Loo, J.K.; Crawley, M.H.; et al. PD-1/PD-L1 blockade enhances T-cell activity and antitumor efficacy of
Imatinib in gastrointestinal stromal tumors. Clin. Cancer Res. 2017, 23, 454–465. [CrossRef][PubMed]
22. Oyer, J.L.; Gitto, S.B.; Altomare, D.A.; Copik, A.J. PD-L1 blockade enhances anti-tumor efficacy of NK cells.
Oncoimmunology 2018, 7, e1509819. [PubMed]
23. Abdel-Wahab, N.; Shah, M.; Lopez-Olivo, M.A.; Suarez-Almazor, M.E. Use of immune checkpoint inhibitors
in the treatment of patients with cancer and preexisting autoimmune disease: A systematic review.
Ann. Intern. Med. 2018, 168, 121–130. [CrossRef][PubMed]
24. Sharma, P.; Allison, J.P. Immune checkpoint targeting in cancer therapy: Toward combination strategies with
curative potential. Cell 2015, 161, 205–214. [CrossRef]
25. Raggi, F.; Pelassa, S.; Pierobon, D.; Penco, F.; Gattorno, M.; Novelli, F.; Eva, A.; Varesio, L.; Giovarelli, M.;
Bosco, M.C. Regulation of human macrophage M1-M2 polarization balance by hypoxia and the triggering
receptor expressed on myeloid cells-1. Front. Immunol. 2017, 8, 1097. [CrossRef]
26. Choi, J.; Gyamfi, J.; Jang, H.; Koo, J.S. The role of tumor-associated macrophage in breast cancer biology.
Histol. Histopathol. 2018, 33, 133–145. [PubMed]
27. Seager, R.J.; Hajal, C.; Spill, F.; Kamm, R.D.; Zaman, M.H. Dynamic interplay between tumour, stroma
and immune system can drive or prevent tumour progression. Converg. Sci. Phys. Oncol. 2017, 3, 034002.
[CrossRef]
28. Tripathi, C.; Tewari, B.N.; Kanchan, R.K.; Baghel, K.S.; Nautiyal, N.; Shrivastava, R.; Kaur, H.; Bhatt, M.L.B.;
Bhadauria, S. Macrophages are recruited to hypoxic tumor areas and acquire a pro-angiogenic M2-polarized
phenotype via hypoxic cancer cell derived cytokines Oncostatin M and Eotaxin. Oncotarget 2014, 5, 5350–5368.
[CrossRef]
29. Williams, C.B.; Yeh, E.S.; Soloff, A.C. Tumor-associated macrophages: Unwitting accomplices in breast cancer
malignancy. NPJ Breast Cancer 2016, 2, 15025. [CrossRef]
30. Luo, H.; Tu, G.; Liu, Z.; Liu, M.; Noy, R.; Pollard, J.W.W. Tumor-associated macrophages: From mechanisms
to therapy. Immunity 2014, 41, 49–61.
31. Hollmén, M.; Roudnicky, F.; Karaman, S.; Detmar, M. Characterization of macrophage—Cancer cell crosstalk
in estrogen receptor positive and triple-negative breast cancer. Sci. Rep. 2015, 5, 9188. [CrossRef][PubMed]
32. Sousa, S.; Brion, R.; Lintunen, M.; Kronqvist, P.; Sandholm, J.; Mönkkönen, J.; Kellokumpu-Lehtinen, P.-L.;
Lauttia, S.; Tynninen, O.; Joensuu, H.; et al. Human breast cancer cells educate macrophages toward the M2
activation status. Breast Cancer Res. 2015, 17, 101. [CrossRef][PubMed]
33. Gubin, M.M.; Esaulova, E.; Ward, J.P.; Malkova, O.N.; Runci, D.; Wong, P.; Noguchi, T.; Arthur, C.D.;
Meng, W.; Alspach, E.; et al. High-dimensional analysis delineates myeloid and lymphoid compartment
remodeling during successful immune-checkpoint cancer therapy. Cell 2018, 175, 1014–1030. [CrossRef]
[PubMed]
34. Su, S.; Liu, Q.; Chen, J.; Chen, J.; Chen, F.; He, C.; Huang, D.; Wu, W.; Lin, L.; Huang, W.; et al. A Positive
feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis.
Cancer Cell 2014, 25, 605–620. [CrossRef]
56
14. Chaudhary, B.; Elkord, E. Regulatory T cells in the tumor microenvironment and cancer progression: Role
and therapeutic targeting. Vaccines 2016, 4, 28. [CrossRef]
15. Fleming, V.; Hu, X.; Weber, R.; Nagibin, V.; Groth, C.; Altevogt, P.; Utikal, J.; Umansky, V. Targeting
myeloid-derived suppressor cells to bypass tumor-induced immunosuppression. Front. Immunol. 2018, 9,
398. [CrossRef]
16. Beyer, M.; Schultze, J.L. Regulatory T cells in cancer. Blood 2006, 108, 804–811. [CrossRef][PubMed]
17. De Visser, K.E.; Eichten, A.; Coussens, L.M. Paradoxical roles of the immune system during cancer
development. Nat. Rev. Cancer 2006, 6, 24–37. [CrossRef][PubMed]
18. Palucka, A.K.; Coussens, L.M. The basis of oncoimmunology. Cell 2016, 164, 1233–1247. [CrossRef]
19. Blank, C.; Mackensen, A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: An update on
implications for chronic infections and tumor evasion. Cancer Immunol. Immunother. 2007, 56, 739–745.
[CrossRef]
20. Jiang, Y.; Li, Y.; Zhu, B. T-cell exhaustion in the tumor microenvironment. Cell Death Dis. 2015, 6, e1792.
[CrossRef]
21. Seifert, A.M.; Zeng, S.; Zhang, J.Q.; Kim, T.S.; Cohen, N.A.; Beckman, M.J.; Medina, B.D.; Maltbaek, J.H.;
Loo, J.K.; Crawley, M.H.; et al. PD-1/PD-L1 blockade enhances T-cell activity and antitumor efficacy of
Imatinib in gastrointestinal stromal tumors. Clin. Cancer Res. 2017, 23, 454–465. [CrossRef][PubMed]
22. Oyer, J.L.; Gitto, S.B.; Altomare, D.A.; Copik, A.J. PD-L1 blockade enhances anti-tumor efficacy of NK cells.
Oncoimmunology 2018, 7, e1509819. [PubMed]
23. Abdel-Wahab, N.; Shah, M.; Lopez-Olivo, M.A.; Suarez-Almazor, M.E. Use of immune checkpoint inhibitors
in the treatment of patients with cancer and preexisting autoimmune disease: A systematic review.
Ann. Intern. Med. 2018, 168, 121–130. [CrossRef][PubMed]
24. Sharma, P.; Allison, J.P. Immune checkpoint targeting in cancer therapy: Toward combination strategies with
curative potential. Cell 2015, 161, 205–214. [CrossRef]
25. Raggi, F.; Pelassa, S.; Pierobon, D.; Penco, F.; Gattorno, M.; Novelli, F.; Eva, A.; Varesio, L.; Giovarelli, M.;
Bosco, M.C. Regulation of human macrophage M1-M2 polarization balance by hypoxia and the triggering
receptor expressed on myeloid cells-1. Front. Immunol. 2017, 8, 1097. [CrossRef]
26. Choi, J.; Gyamfi, J.; Jang, H.; Koo, J.S. The role of tumor-associated macrophage in breast cancer biology.
Histol. Histopathol. 2018, 33, 133–145. [PubMed]
27. Seager, R.J.; Hajal, C.; Spill, F.; Kamm, R.D.; Zaman, M.H. Dynamic interplay between tumour, stroma
and immune system can drive or prevent tumour progression. Converg. Sci. Phys. Oncol. 2017, 3, 034002.
[CrossRef]
28. Tripathi, C.; Tewari, B.N.; Kanchan, R.K.; Baghel, K.S.; Nautiyal, N.; Shrivastava, R.; Kaur, H.; Bhatt, M.L.B.;
Bhadauria, S. Macrophages are recruited to hypoxic tumor areas and acquire a pro-angiogenic M2-polarized
phenotype via hypoxic cancer cell derived cytokines Oncostatin M and Eotaxin. Oncotarget 2014, 5, 5350–5368.
[CrossRef]
29. Williams, C.B.; Yeh, E.S.; Soloff, A.C. Tumor-associated macrophages: Unwitting accomplices in breast cancer
malignancy. NPJ Breast Cancer 2016, 2, 15025. [CrossRef]
30. Luo, H.; Tu, G.; Liu, Z.; Liu, M.; Noy, R.; Pollard, J.W.W. Tumor-associated macrophages: From mechanisms
to therapy. Immunity 2014, 41, 49–61.
31. Hollmén, M.; Roudnicky, F.; Karaman, S.; Detmar, M. Characterization of macrophage—Cancer cell crosstalk
in estrogen receptor positive and triple-negative breast cancer. Sci. Rep. 2015, 5, 9188. [CrossRef][PubMed]
32. Sousa, S.; Brion, R.; Lintunen, M.; Kronqvist, P.; Sandholm, J.; Mönkkönen, J.; Kellokumpu-Lehtinen, P.-L.;
Lauttia, S.; Tynninen, O.; Joensuu, H.; et al. Human breast cancer cells educate macrophages toward the M2
activation status. Breast Cancer Res. 2015, 17, 101. [CrossRef][PubMed]
33. Gubin, M.M.; Esaulova, E.; Ward, J.P.; Malkova, O.N.; Runci, D.; Wong, P.; Noguchi, T.; Arthur, C.D.;
Meng, W.; Alspach, E.; et al. High-dimensional analysis delineates myeloid and lymphoid compartment
remodeling during successful immune-checkpoint cancer therapy. Cell 2018, 175, 1014–1030. [CrossRef]
[PubMed]
34. Su, S.; Liu, Q.; Chen, J.; Chen, J.; Chen, F.; He, C.; Huang, D.; Wu, W.; Lin, L.; Huang, W.; et al. A Positive
feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis.
Cancer Cell 2014, 25, 605–620. [CrossRef]
56