Immunoscore: a novel prognostic tool. Association with clinical outcome, response to treatment and survival in several malignancies

Ros-Martínez, Silverio; Navas-Carrillo, Diana; Alonso-Romero, José Luis; Orenes‐Piñero, Esteban

doi:10.1080/10408363.2020.1729692

Cited by 26 publications

(24 citation statements)

References 56 publications

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“…20,29 Overall, TIL localization (CT versus IM) was unavailable in previous studies, 19,21,22 an understanding of which could be essential to optimizing the prognostic value of an IS for NSCLC. 20,29 A recent study by Ishii et al that accounted for TIL localization included a relatively small number of patients for the analysis. 32 In the present study, we found that evaluation of CD45RO+ T cells and CD8+ T cells in combined tumor regions (CT and IM) allowed successful stratification of patients into two prognostic categories with dramatically different DMFS and OS prognoses.…”

Section: Discussionmentioning

confidence: 99%

Clinical impact of the tumor immune microenvironment in completely resected stage IIIA(N2) non-small cell lung cancer based on an immunological score approach

Feng

Shen

et al. 2021

Ther Adv Med Oncol

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Background: Completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC) comprises a heterogeneous population according to discrepancies in survival prognosis. Accumulating evidence suggests that tumor-infiltrating lymphocytes (TILs) are clinically significant, despite a lack of consensus regarding the immunoscore (IS) in NSCLC. Here, we determined the prognostic value of the immune microenvironment as an IS in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC. Methods: Consecutive patients with pathologically confirmed stage IIIA(N2) NSCLC and who underwent complete resection (2005–2012) were retrospectively reviewed. Tissue microarrays (TMAs) were constructed from surgical paraffin-embedded primary lung tumor specimen. For each case, two representative regions from the tumor center (CT) and two from the invasive margin (IM) containing the highest density of lymphocytes were selected. Densities of CD3+, CD45RO+, and CD8+ lymphocytes were assessed using immunohistochemistry (IHC) by specialized pathologists according to predefined scoring scales. Patients were classified according to IS definition based on TIL type, density, and distribution, and relationships between IS and prognosis were evaluated. Results: Patients ( N = 288) with complete IHC-based TMA spots were included. Univariate analyses showed that CD3+ T cell density was associated with neither overall survival (OS) nor distant metastasis-free survival (DMFS), whereas CD45RO+ T cell density in the IM was a significant prognostic factor for DMFS ( p = 0.02) and was predictive of OS ( p = 0.05). Combined CD45RO+ and CD8+ cell infiltration in tumor regions (CT and IM) significantly improved IS prognostic impact. Multivariate analyses revealed IS as an independent prognostic predictor for both DMFS ( p = 0.001) and OS ( p = 0.002). Conclusion: The proposed IS might provide valuable prognostic information, including prediction of DMFS and OS in stage IIIA(N2) NSCLC patients. Larger patient cohorts are needed to validate this IS classification, which might assist with accurate risk stratification and treatment decisions.

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Section: Discussionmentioning

confidence: 99%

Clinical impact of the tumor immune microenvironment in completely resected stage IIIA(N2) non-small cell lung cancer based on an immunological score approach

Feng

Shen

et al. 2021

Ther Adv Med Oncol

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“…To this end, investigators have proposed an alternative score, the "immuno-score" that calculates CD3+ and CD8+ T cells in the center and invasive margin of the tumor, which may further stratify outcomes of patients with HCC [25,26]. Although the predictive ability of this score has been validated in a number of malignancies [25,27], information on tumor cell infiltration was not available in the current dataset. In turn, further analysis on the association of the immuno-score and the combination of TBS/AFP relative to patient outcomes was not possible in this study.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Impact of Alpha-Fetoprotein and Tumor Burden on Long-Term Outcomes Following Curative-Intent Resection of Hepatocellular Carcinoma

Tsilimigras

Hyer

Díaz

et al. 2021

Cancers

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Introduction: The prognostic role of tumor burden score (TBS) relative to pre-operative α -fetoprotein (AFP) levels among patients undergoing curative-intent resection of HCC has not been examined. Methods: Patients who underwent curative-intent resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS on overall survival (OS) and cumulative recurrence relative to serum AFP levels was assessed. Results: Among 898 patients, 233 (25.9%) patients had low TBS, 572 (63.7%) had medium TBS and 93 (10.4%) had high TBS. Both TBS (5-year OS; low TBS: 76.9%, medium TBS: 60.9%, high TBS: 39.1%) and AFP (>400 ng/mL vs. <400 ng/mL: 48.5% vs. 66.1%) were strong predictors of outcomes (both p < 0.001). Lower TBS was associated with better OS among patients with both low (5-year OS, low–medium TBS: 68.0% vs. high TBS: 47.7%, p < 0.001) and high AFP levels (5-year OS, low–medium TBS: 53.7% vs. high TBS: not reached, p < 0.001). Patients with low–medium TBS/high AFP had worse OS compared with individuals with low–medium TBS/low AFP (5-year OS, 53.7% vs. 68.0%, p = 0.003). Similarly, patients with high TBS/high AFP had worse outcomes compared with patients with high TBS/low AFP (5-year OS, not reached vs. 47.7%, p = 0.015). Patients with high TBS/low AFP and low TBS/high AFP had comparable outcomes (5-year OS, 47.7% vs. 53.7%, p = 0.24). The positive predictive value of certain TBS groups relative to the risk of early recurrence and 5-year mortality after HCC resection increased with higher AFP levels. Conclusion: Both TBS and serum AFP were important predictors of prognosis among patients with resectable HCC. Serum AFP and TBS had a synergistic impact on prognosis following HCC resection with higher serum AFP predicting worse outcomes among patients with HCC of a certain TBS class.

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“…The immune and stromal score are derived from the immune contexture, and is defined by immune cell infiltration based on ssGSEA. Several studies have proved that higher immune/stromal score are associated with favorable prognosis of human malignancies, such as hepatocellular carcinoma, pancreatic cancer, melanoma, and lung cancer ( 10 ). It was suggested that insufficient immune infiltration of T2 might lead to failures in tumor immune surveillance and trigger tumor immune escape.…”

Section: Discussionmentioning

confidence: 99%

Case Report: A Rare Case of Metachronous Multiple Primary Lung Cancers in a Patient With Successful Management by Switching From Anti-PD-1 Therapy to Anti-PD-L1 Therapy

Lin

Qiu

Li³

et al. 2021

Front. Immunol.

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Without global standard diagnostic criteria, distinguishing multiple primary lung cancers (MPLCs) from intrapulmonary metastasis or histologic transformation has been a big challenge in clinical practice. Here, we described a rare case of metachronous adenocarcinoma and small cell lung cancer (SCLC) in a patient who developed drug resistance to pembrolizumab. Both DNA-sequencing and RNA-sequencing were performed on primary adenocarcinoma and resistant lesions. Through the comparison of primary adenocarcinoma and novel lesion mutation profiles, along with bioinformatic estimation of immune proportion by using RNA sequence data, we revealed the origin and tumor microenvironment of the two lesions. No shared mutations were detected between lung adenocarcinoma (LUAD) and SCLC from the same patient, suggesting these two lesions might be from separate primary lung cancers. Compared to LUAD, SCLC showed a relatively cold microenvironment, including negative PD-L1. The patient obtained durable clinical benefits upon treatment with atezolizumab, without experiencing immune-related adverse events. Disease progression should be monitored with prompt re-biopsy and molecular profiling to spot a potential histologic change and to shed light on therapeutic alternatives. The use of atezolizumab, either alone or in combination with other agents, may be a potential therapeutic strategy for patients with both LUAD and SCLC.

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Immunoscore: a novel prognostic tool. Association with clinical outcome, response to treatment and survival in several malignancies

Cited by 26 publications

References 56 publications

Clinical impact of the tumor immune microenvironment in completely resected stage IIIA(N2) non-small cell lung cancer based on an immunological score approach

Clinical impact of the tumor immune microenvironment in completely resected stage IIIA(N2) non-small cell lung cancer based on an immunological score approach

Synergistic Impact of Alpha-Fetoprotein and Tumor Burden on Long-Term Outcomes Following Curative-Intent Resection of Hepatocellular Carcinoma

Case Report: A Rare Case of Metachronous Multiple Primary Lung Cancers in a Patient With Successful Management by Switching From Anti-PD-1 Therapy to Anti-PD-L1 Therapy

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