An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer

Karasaki, Takahiro; Nagayama, Kazuhiro; Kuwano, Hideki; Nitadori, Jun-ichi; Sato, Masaaki; Anraku, Masaki; Hosoi, Akihiro; Matsushita, Hirokazu; Morishita, Yasuyuki; Kashiwabara, Kosuke; Takazawa, Masaki; Ohara, Osamu; Kakimi, Kazuhiro; Nakajima, Jun

doi:10.1016/j.jtho.2017.01.005

Cited by 130 publications

(100 citation statements)

References 36 publications

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“…Our results highlight the prospect that anti‐MARCO treatment could improve the response of available immune‐modulatory drugs. It is likely that macrophage profiling will form one important axis in future multimodal predictive testing for personalized immunotherapy …”

Section: Discussionmentioning

confidence: 99%

Expression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer

Fleur

Boura

Alexeyenko

et al. 2018

Intl Journal of Cancer

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Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n = 352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n = 199) with available RNA-seq data. We observed a large variation in macrophage density between cases and a strong correlation between CD68 and CD163, suggesting that the majority of TAMs present in NSCLC exhibit a protumor phenotype. Correlation to clinical data only showed a weak trend toward worse survival for patients with high macrophage infiltration. Interestingly, MARCO was expressed on a distinct subpopulation of TAMs, which tended to aggregate in close proximity to tumor cell nests. On the transcriptomic level, we found a positive association between MARCO gene expression and general immune response pathways including strong links to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules. Indeed, a higher macrophage infiltration was seen in tumors expressing PD-L1, and macrophages residing within tumor cell nests co-expressed MARCO and PD-L1. Thus, MARCO is a potential new immune target for anti-TAM treatment in a subset of NSCLC patients, possibly in combination with available immune checkpoint inhibitors.

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Section: Discussionmentioning

confidence: 99%

Expression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer

Fleur

Boura

Alexeyenko

et al. 2018

Intl Journal of Cancer

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“…It may be necessary to combine multiple biomarkers that capture different aspects of the tumor-immune cell interaction in order to accurately predict the response to ICIs. Cancer immunograms are one method for integrating biomarkers and have been applied to lung cancer patients to identify different phenotypes [102]. Immunograms build a picture of the patient-specific tumor microenvironment and have the potential to be utilized for optimal personalized immunotherapy [102,103].…”

Section: Future Perspectivementioning

confidence: 99%

“…Cancer immunograms are one method for integrating biomarkers and have been applied to lung cancer patients to identify different phenotypes [102]. Immunograms build a picture of the patient-specific tumor microenvironment and have the potential to be utilized for optimal personalized immunotherapy [102,103]. This paper has focused on the use of PD-1/PD-L1 inhibitors as monotherapy as this is most relevant to clinical practice at this time.…”

Section: Future Perspectivementioning

confidence: 99%

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a standard treatment option for patients with advanced non-small-cell lung cancer. However, a substantial proportion of patients will not benefit from these treatments, and robust biomarkers are required to help clinicians select patients who are most likely to benefit. Here, we discuss the available evidence on the utility of clinical characteristics in the selection of patients with advanced non-small-cell lung cancer as potential candidates for single-agent anti-PD-1/PD-L1 therapy, and provide practical guidance to clinicians on identifying those patients who are most likely to benefit. Recommendations on the use of immune checkpoint inhibitor in clinically challenging populations are also provided.

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“…Currently, the main treatment methods for lung cancer include surgical and non‐surgical treatment; non‐surgical treatment consists of radiotherapy, chemotherapy, and immunity and molecular targeted drugs. However, there are many defects in both individual and comprehensive treatment schemes . Therefore, new and targeted drug research is the current focus for the prevention and treatment of lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Hydroxysafflor yellow A inhibited lipopolysaccharide‐induced non‐small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

Jiang

Zhou

et al. 2019

Thoracic Cancer

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Background Chronic inflammation plays a significant role in the occurrence and development of non‐small cell lung cancer (NSCLC). Hydroxysafflor yellow A (HSYA), a chemical compound of the yellow color pigments extracted from the safflower, has been widely used in clinical treatment with positive antioxidation, anti‐inflammation, and antitumor effects. However, the role and underlying mechanisms of HYSA on development and progress in inflammation‐mediated NSCLC are unknown. Methods Cell counting kit‐8, colony formation, EdU, cell apoptosis, wound healing, Transwell migration and invasion, and enzyme‐linked immunosorbent assays; flow cytometry; and Western blotting were conducted using human NSCLC cell lines A549 and H1299. Results Lipopolysaccharide (LPS) significantly promoted the proliferation and enhanced colony formation of A549 and H1299 cells, while HYSA notably reversed the effects of LPS. HYSA induced apoptosis of LPS‐mediated A549 and H1299 cells in a dose dependent manner; and remarkably suppressed migration, invasion, and epithelial–mesenchymal transition (EMT), significantly regulated production of LPS‐induced inflammation cytokines, and downregulated protein expression of PI3K/Akt/mTOR and ERK/MAPK signaling pathways in LPS‐induced A549 and H1299 cells. Furthermore, PI3K (LY294002) and ERK (SCH772984) inhibitors remarkably inhibited proliferation, migration, invasion, and EMT, and induced apoptosis in LPS‐mediated A549 and H1299 cells. These effects were even more obvious in the presence of HYSA and LY294002 or SCH772984 compared to those of either agent alone. Conclusion HYSA suppressed LPS‐mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation‐mediated NSCLC.

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An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer

Abstract: The patient-specific landscape of the tumor microenvironment can be appreciated by using immunograms as integrated biomarkers, which may thus become a valuable resource for optimal personalized immunotherapy.

Cited by 130 publications

References 36 publications

Expression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer

Expression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

Hydroxysafflor yellow A inhibited lipopolysaccharide‐induced non‐small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

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