Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy

Loo, Kimberly; Tsai, Katy K.; Mahuron, Kelly; Liu, Jacqueline; Pauli, Mariela; Sandoval, Priscila Muñoz; Nosrati, Adi; Lee, James; Chen, Lawrence R.; Hwang, Jimmy J.; Levine, Lauren P.; Krummel, Matthew F.; Algazi, Alain P.; Pampaloni, Miguel Hernandez; Alvarado, Michael; Rosenblum, Michael D.; Daud, Adil

doi:10.1172/jci.insight.93433

Cited by 68 publications

(47 citation statements)

References 40 publications

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“…Moreover, the immune inhibitory liver environment can also contribute to increased therapy resistance. In agreement with this notion, reduced T cell infiltration and low levels of PD-1 + CTLA-4 + tumor-infiltrating CD8 T cells were linked to poor outcomes in liver metastasis patients [103]. These results suggest that further disruption of the metastatic immunosuppressive environment, either by combination therapies or by locoregionary approaches, could augment outcomes in these settings.…”

Section: Icb As Treatment Options For Liver Cancersupporting

confidence: 69%

Success of immune checkpoint blockade therapies – mechanisms and implications for hepatology

Bengsch

Thimme

2019

Z Gastroenterol

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The success of immune modulation by checkpoint blockade approaches is currently transforming oncology, with high and long-lasting tumor responses in patients with advanced disease across many cancer entities. Rooted in the reinvigoration of adaptive antitumor immune responses through disinhibition of negative feedback pathways, these approaches are particularly effective in patients with significant preexisting T cell responses in tumors with high neoantigen load. While promising data is starting to emerge from clinical trials in liver cancer patients, the underlying immunobiology remains poorly understood. In this review, we discuss the immunological mechanisms underlying the success of current checkpoint blockade therapies and the implications for hepatology including management of immune-related hepatitis. Checkpoint blockade therapy provides novel therapeutic options for difficult-to-treat liver cancers but also novel clinical challenges for hepatologists facing immune-related adverse events.

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Section: Icb As Treatment Options For Liver Cancersupporting

confidence: 69%

Success of immune checkpoint blockade therapies – mechanisms and implications for hepatology

Bengsch

Thimme

2019

Z Gastroenterol

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“…One last consideration may lie within the distinct metastatic pattern of UM and its predilection for the liver. The liver itself has also been described as a site of immune privilege, and metastasis here may exert a peripheral tolerance and reduce the likelihood of a robust response to immunotherapy …”

Section: Challenges Of Immunotherapymentioning

confidence: 99%

Obstacles to improving outcomes in the treatment of uveal melanoma

Tsai

Bollin

Patel

2018

Cancer

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The rate of advances in uveal melanoma has not kept pace with the rate of advances in cutaneous melanoma. Many patients lack access to or knowledge of specialty centers, and integrated multidisciplinary care between ophthalmology, radiation oncology, and medical oncology is far from the norm. This treatment isolation leads to limited communication about novel clinical trial opportunities. Clinical trials themselves are not widely available, and a lack of robust funding limits rapid and complete investigations. This review outlines the obstacles to success in uveal melanoma management and highlights strategies for overcoming these challenges. Cancer 2018;124:2693-2703. © 2018 American Cancer Society.

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“…Systemic immune response coordinated across tissues has been observed to be essential to tumor rejection [213] . The fraction of tumor-infiltrating partially exhausted cytotoxic T lymphocytes (peCTLs) correlates with response to anti-PD-1 monotherapy, with a low fraction indicating the use of combination checkpoint blockade therapy [214] . A possible implication is that checkpoint blockade therapy is most effective when the immune system has already mounted a tumor-specific if suppressed response.…”

Section: Monitoring and Modelingmentioning

confidence: 99%

A primer on recent developments in cancer immunotherapy, with a focus on neoantigen vaccines

Tokuyasu¹,

Huang²

2018

JCMT

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Cancer immunotherapy has now been conclusively shown to be capable of producing durable responses for a substantial number of patients. Adoptive cell transfer and checkpoint blockade therapies in particular both demonstrate that antigen-specific immune responses can be dramatically effective, even in previously refractory late stage disease. Such developments, together with advances in technology, have strongly encouraged revisiting the concept of neoantigen vaccines. Here we introduce basic ideas in the field to allow investigators from diverse backgrounds to understand these developments, grasp current issues, and contribute to further progress.

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Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy

Cited by 68 publications

References 40 publications

Success of immune checkpoint blockade therapies – mechanisms and implications for hepatology

Success of immune checkpoint blockade therapies – mechanisms and implications for hepatology

Obstacles to improving outcomes in the treatment of uveal melanoma

A primer on recent developments in cancer immunotherapy, with a focus on neoantigen vaccines

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