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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Immune and molecular correlates in melanoma treated with immune checkpoint blockade
Elizabeth H Byrne1, David E Fisher1
1Department of Dermatology and Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Abstract:
Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic melanoma is now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility complex class I expression, mutational load in the tumor, and T-cell infiltration into the tumor. In addition, clinical correlates of response, notably vitiligo and other immune-related adverse events, can potentially shed light on the mechanisms by which checkpoint blockade may achieve such great success, particularly in melanoma. The authors propose that microphthalmia-associated transcription factor-a key regulator of melanocyte survival, melanin production, and melanoma transformation-produces a molecular landscape in melanocytes and melanoma cells that can make melanomas particularly susceptible to checkpoint blockade and also can result in immune attack on normal melanocytes. Cancer 2017;123:2143-53. © 2017 American Cancer Society.
Insights
Checkpoint inhibitors offer durable remission for metastatic melanoma. Molecular indicators like PD-L1 expression and tumor mutational load predict patient response to this immunotherapy.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Immunotherapy, particularly checkpoint inhibitors, has transformed metastatic melanoma treatment.
- While effective, predicting patient response to checkpoint blockade remains a challenge.
Purpose of the Study:
- To review molecular and clinical indicators of response to checkpoint inhibition in metastatic melanoma.
- To explore the role of microphthalmia-associated transcription factor (MITF) in melanoma's susceptibility to immunotherapy.
Main Methods:
- Review of literature on immunotherapy for metastatic melanoma.
- Focus on molecular markers: programmed death ligand 1 (PD-L1) expression, major histocompatibility complex class I (MHC-I) expression, tumor mutational load, and T-cell infiltration.
- Analysis of clinical correlates such as vitiligo and immune-related adverse events.
Main Results:
- Several molecular factors influence response to checkpoint inhibitors in melanoma.
- Tumor PD-L1 expression, MHC-I expression, mutational load, and T-cell infiltration are key indicators.
- Clinical signs like vitiligo may correlate with treatment efficacy.
Conclusions:
- Melanoma's unique molecular profile, influenced by MITF, may enhance susceptibility to checkpoint blockade.
- Understanding these indicators can optimize immunotherapy strategies for metastatic melanoma.
- MITF may contribute to both melanoma's response to immunotherapy and autoimmune attack on melanocytes.
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