2019
DOI: 10.3390/cancers11050628
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Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

Abstract: Cancer immunotherapy has altered the management of human malignancies, improving outcomes in an expanding list of diseases. Breast cancer - presumably due to its perceived low immunogenicity - is a late addition to this list. Furthermore, most of the focus has been on the triple negative subtype because of its higher tumor mutational load and lymphocyte-enriched stroma, although emerging data show promise on the other breast cancer subtypes as well. To this point the clinical use of immunotherapy is limited to… Show more

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Cited by 58 publications
(58 citation statements)
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References 353 publications
(311 reference statements)
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“…[37][38][39] These observations could indicate that different immune checkpoint axes other than PD-1 or CTLA-4 may be more relevant and therefore better targets in breast cancer. 40 Our present study provides strong evidence that the PVR-TIGIT axis may represent a promising therapeutic target for breast cancer patients.…”
Section: Discussionsupporting
confidence: 56%
“…[37][38][39] These observations could indicate that different immune checkpoint axes other than PD-1 or CTLA-4 may be more relevant and therefore better targets in breast cancer. 40 Our present study provides strong evidence that the PVR-TIGIT axis may represent a promising therapeutic target for breast cancer patients.…”
Section: Discussionsupporting
confidence: 56%
“…Unlike immunologically "hot" tumors such as lung cancer, melanoma, and bladder cancer, most breast carcinomas are not inherently immunogenic. Consequently, they typically exhibit low T-cell infiltration and are unlikely to benefit from immune checkpointcentric therapies [1][2][3][4][5]. Exceptions to this immunologically "cold" rule of breast carcinomas are the socalled basal-like [6][7][8][9][10][11][12][13][14] and HER2-positive [15][16][17][18][19][20] subtypes, both of which show evidence of immunogenicity including tumor immune infiltrates and stromal and intratumoral tumor-infiltrating lymphocytes, a good predictive marker for responses to immunotherapy.…”
Section: Introductionmentioning
confidence: 99%
“…[7][8][9] Despite promising, the TNBC patients rarely benefit from current ICB therapy due to low immunogenicity and immunosuppressive tumor micro environment (ITM) of TNBC tumors. [10][11][12][13][14][15][16] Thus, complementary approaches to enhance the immunogenicity and reverse the ITM remain a formidable challenge for improving immunotherapy of TNBC. [17][18][19][20] The combination of ICB therapy with chemotherapy, photodynamic therapy (PDT) or radiotherapy has displayed synergistic antitumor effect to facilitate intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and overcome the ITM.…”
mentioning
confidence: 99%