A Subset of PD-1-Expressing CD56bright NK Cells Identifies Patients with Good Response to Immune Checkpoint Inhibitors in Lung Cancer

Ruiz, Marta Gascón; Ramírez-Labrada, Ariel; Lastra, Rodrigo Pimienta; Martínez-Lostao, Luis; Paño‐Pardo, José Ramón; Sesma, Andrea; Zapata-Garcia, Maria; Moratiel, Alba; Quilez, Elisa; Torres-Ramón, Irene; Yubero, A.; Domingo, María Pilar; Esteban, Patricia; Gálvez, Eva M.; Pardo, Julián; Isla, Dolores

doi:10.3390/cancers15020329

Cited by 13 publications

(9 citation statements)

References 62 publications

(71 reference statements)

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“…This result indicates that NK CD56 brigh cells are not responsive to anti-PD-1 therapy and suggests that PD-1 expression on NK CD56 brigh cells could be upregulated by a compensatory mechanism triggered by therapy and could be related to response to therapy and/or vitiligo development. Consistently, it has been demonstrated a positive correlation between PD-1 expression on NK CD56 brigh cells and overall survival of patients with lung cancer undergoing immunotherapy ( 44 ). However, a higher number of patients should be considered to clarify this point.…”

Section: Discussionmentioning

confidence: 67%

Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy

Carbone,

Capone,

Guercio

et al. 2023

Front. Immunol.

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IntroductionImmunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a detailed characterization of immune cells during vitiligo onset in melanoma patients would give insight into the immune mechanisms mediating both the irAE and the anti-tumor response. MethodsTo better understand these aspects, we analyzed T cell subsets from peripheral blood of metastatic melanoma patients undergoing treatment with anti-programmed cell death protein (PD)-1 antibodies. To deeply characterize the antitumoral T cell response concomitant to vitiligo onset, we analyzed T cell content in skin biopsies collected from melanoma patients who developed vitiligo. Moreover, to further characterize T cells in vitiligo skin lesion of melanoma patients, we sequenced T cell receptor (TCR) of cells derived from biopsies of vitiligo and primary melanoma of the same patient.Results and discussionStratification of patients for developing or not developing vitiligo during anti-PD-1 therapy revealed an association between blood reduction of CD8-mucosal associated invariant T (MAIT), T helper (h) 17, natural killer (NK) CD56bright, and T regulatory (T-reg) cells and vitiligo onset. Consistently with the observed blood reduction of Th17 cells in melanoma patients developing vitiligo during immunotherapy, we found high amount of IL-17A expressing cells in the vitiligo skin biopsy, suggesting a possible migration of Th17 cells from the blood into the autoimmune lesion. Interestingly, except for a few cases, we found different TCR sequences between vitiligo and primary melanoma lesions. In contrast, shared TCR sequences were identified between vitiligo and metastatic tissues of the same patient. These data indicate that T cell response against normal melanocytes, which is involved in vitiligo onset, is not typically mediated by reactivation of specific T cell clones infiltrating primary melanoma but may be elicited by T cell clones targeting metastatic tissues. Altogether, our data indicate that anti-PD-1 therapy induces a de novo immune response, stimulated by the presence of metastatic cells, and composed of different T cell subtypes, which may trigger the development of vitiligo and the response against metastatic tumor.

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Section: Discussionmentioning

confidence: 67%

Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy

Carbone,

Capone,

Guercio

et al. 2023

Front. Immunol.

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“…Predictive markers have also been searched in the immune cell profiling [ 25 ], concluding that lymphocyte and NK cell populations are of great interest. However, no immune cell profile has yet been identified with sufficient clinical relevance to be established in clinical practice.…”

Section: Resultsmentioning

confidence: 99%

Biomarkers of Immunotherapy Response in Patients with Non-Small-Cell Lung Cancer: Microbiota Composition, Short-Chain Fatty Acids, and Intestinal Permeability

Moratiel-Pellitero,

Zapata-García,

Gascón-Ruiz

et al. 2024

Cancers

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Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host–microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients’ microbial gut ecosystems were rich and diverse, and the intestinal barrier’s integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.

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“…Growing studies have demonstrated that lymphocytes and NK cells are key roles in immune defense against tumor cells. A recent prospective study has identified a subset of circulating CD56+CD16‐PD‐1+ NK cells showing good predictive ability to ICIs response in NSCLC patients with immunotherapy 123 . In addition, considering cancer patients commonly inhibit deficiency in NK cells, growing evidence has indicated that adoptive transfer of NK cells could be a useful immunotherapy tool across a number of solid cancers 124–126 .…”

Section: Circulating Immune Cells In Antitumor Immunotherapymentioning

confidence: 99%

“…A recent prospective study has identified a subset of circulating CD56+CD16‐PD‐1+ NK cells showing good predictive ability to ICIs response in NSCLC patients with immunotherapy. 123 In addition, considering cancer patients commonly inhibit deficiency in NK cells, growing evidence has indicated that adoptive transfer of NK cells could be a useful immunotherapy tool across a number of solid cancers. 124 , 125 , 126 And beyond immunotherapy, researchers suggest that molecularly targeted agents can elicit NK cell‐mediated antitumor immunity, providing further evidence that NK cells will play an increasingly key role in cancer treatment.…”

Section: Circulating Immune Cells In Antitumor Immunotherapymentioning

confidence: 99%

Progresses in biomarkers for cancer immunotherapy

Lin,

Zong,

Zhang

et al. 2023

MedComm

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Currently, checkpoint inhibitor‐based immunotherapy has emerged as prevailing treatment modality for diverse cancers. However, immunotherapy as a first‐line therapy has not consistently yielded durable responses. Moreover, the risk of immune‐related adverse events increases with combination regimens. Thus, the development of predictive biomarkers is needed to optimize individuals benefit, minimize risk of toxicities, and guide combination approaches. The greatest focus has been on tumor programmed cell death‐ligand 1 (PD‐L1), microsatellite instability (MSI), and tumor mutational burden (TMB). However, there remains a subject of debate due to thresholds variability and significant heterogeneity. Major unmet challenges in immunotherapy are the discovery and validation of predictive biomarkers. Here, we show the status of tumor PD‐L1, MSI, TMB, and emerging data on novel biomarker strategies with oncogenic signaling and epigenetic regulation. Considering the exploration of peripheral and intestinal immunity has served as noninvasive alternative in predicting immunotherapy, this review also summarizes current data in systemic immunity, encompassing solute PD‐L1 and TMB, circulating tumor DNA and infiltrating lymphocytes, routine emerging inflammatory markers and cytokines, as well as gut microbiota. This review provides up‐to‐date information on the evolving field of currently available biomarkers in predicting immunotherapy. Future exploration of novel biomarkers is warranted.

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A Subset of PD-1-Expressing CD56bright NK Cells Identifies Patients with Good Response to Immune Checkpoint Inhibitors in Lung Cancer

Cited by 13 publications

References 62 publications

Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy

Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy

Biomarkers of Immunotherapy Response in Patients with Non-Small-Cell Lung Cancer: Microbiota Composition, Short-Chain Fatty Acids, and Intestinal Permeability

Progresses in biomarkers for cancer immunotherapy

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