Accumulated studies have provided controversial evidences of the association between signal transducer and activator of transcription proteins 3 (STAT3) expression and survival of human solid tumors. To address this inconsistency, we performed a meta-analysis with 63 studies identified from PubMed, Medline and EBSCO. We found STAT3 overexpression was significantly associated with worse 3-year overall survival (OS) (OR = 2.06, 95% CI = 1.57 to 2.71, P < 0.00001) and 5-year OS (OR = 2.00, 95% CI = 1.53 to 2.63, P < 0.00001) of human solid tumors. Similar results were observed when disease free survival (DFS) were analyzed. Subgroup analysis showed that elevated STAT3 expression was associated with poor prognosis of gastric cancer, lung cancer, gliomas, hepatic cancer, osteosarcoma, prostate cancer, pancreatic cancer but better prognosis of breast cancer. The correlation between STAT3 and survival of solid tumors was related to its phosphorylated state. High expression level of STAT3 was also associated with advanced tumor stage. In conclusion, elevated STAT3 expression is associated with poor survival in most solid tumors. STAT3 is a valuable biomarker for prognosis prediction and a promising therapeutic target in human solid tumors.

BackgroundTumor-associated macrophages (TAMs) play a crucial role in the regulation of local inflammatory and immune response of tumor microenvironment, being associated with worse outcome of several solid tumors. But the prognostic value of tumor-infiltrating TAMs in lung cancer is still controversial.MethodsWe conduct a meta-analysis of 3055 patients in 21 studies searched from PubMed and Medline to investigate the correlation between tumor-infiltrating TAMs, including distinct TAM subsets and tissue distribution, and survival of lung cancer. Survival data were computed into odds ratios (ORs) and pooled using Mantel–Haenszel random-effect model. All statistical tests were two-sided.ResultsHigh density of tumor-infiltrating TAMs was significantly associated with worse overall survival (OS) at 3 years (OR = 2.45, 95% CI = 1.25 to 4.80, P = 0.009) and 5 years (OR = 2.04, 95% CI = 1.03 to 4.01, P = 0.04) of lung cancer. Results for disease free survival (DFS) were similar. M2 subset was associated with worse 3 year-OS and 5 year-OS, whereas M1 subset was associated with better 3-year OS and 5-year OS. Elevated TAM density in tumor stroma was associated with worse OS at 3 years and 5 years, while elevated TAMs in tumor islet/tumor stroma were associated with better OS at 3 years and 5 years.ConclusionsIncreased tumor-infiltrating TAMs are associated with poor prognosis of lung cancer. M2 subset and TAMs in tumor stroma were associated with worse survival, while M1 subset and TAMs in tumor islet were associated with favorable survival of lung cancer.

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Background: NKG2A is an inhibitory receptor of both T cells and natural killer (NK) cells. Persistent activation promotes T cells and NK cells to express NKG2A and results in the progression of chronic infection and cancer. However, the characteristics and subsets of NKG2A + lymphocytes in human lung cancer are still unclear.Methods: Here, we used the Tumor Immune Estimation Resource database and immune profiling of paired biospecimens to uncover the correlation between NKG2A expression and immune infiltration levels in human cancer as well as the characteristics of NKG2A + lymphocytes in human lung cancer.Results: We found that KLRC1 expression was especially correlated with CD8 + T-cell infiltration levels in 34 types of human cancer through the Tumor Immune Estimation Resource database. Moreover, NKG2A + CD8 + T cells were the predominant subset of NKG2A + lymphocytes in human lung cancer. In contrast, the NKG2A + NK cells were decreased in tumors compared with the paired normal lung tissue. Tumor-infiltrating NKG2A + CD8 + T cells expressed tissue-resident memory T cell (T RM cell) and exhausted T-cell markers. Cytokines and cytotoxic molecules secreted by tumor-infiltrating NKG2A + CD8 + T cells were significantly lower than those secreted by NKG2A − CD8 + T cells in vitro. When stimulated with T-cell receptor activator, tumor-infiltrating NKG2A + CD8 + T cells could secrete large amounts of granzyme B.Conclusions: Our findings demonstrate that tumor-infiltrating NKG2A + CD8 + T cells form the predominant subset of NKG2A + cells in human lung cancer and suggest that targeting NKG2A + CD8 + T cells is a promising approach for future anti-lung cancer immunotherapy.

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8500 Background: Neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy have a promising efficacy in resectable non-small-cell lung cancer (NSCLC), yet the period of neoadjuvant immunochemotherapy is undetermined. This phase II study compared the efficacy and safety of two cycles with three cycles of neoadjuvant sintilimab plus chemotherapy in resectable stage IB-IIIA NSCLC. Methods: This randomized, open-label phase II trial recruited patients aged 18 or older with histologically confirmed, treatment-naïve, American Joint Committee on Cancer-defined stage IB-IIIA, resectable NSCLC. Eligible patients were randomly assigned to two or three cycles of neoadjuvant treatment with intravenous sintilimab (200 mg) plus carboplatin (area under curve 5) and nab-paclitaxel (260mg/m2, for squamous) or pemetrexed (500mg/m2, for non-squamous) on day 1 of three-week cycle. After surgical resection, patients received totally four doses of perioperative immunochemotherapy, followed by one-year sintilimab maintenance under patient decision. Randomisation was stratified by tumor PD-L1 expression (≥1% vs < 1%). The primary endpoint was MPR rate. Secondary endpoints included complete pathology response (pCR) rate, objective response rate (ORR), 2-year disease-free survival (DFS) rate, 2-year overall survival (OS) rate and safety. This trial is registered with ClinicalTrials.gov, number: NCT04459611. Results: From 6/2020 to 9/2021, 60 patients were enrolled and received neoadjuvant treatment. The patient characteristics of both arms were well balanced. Among 55 patients with successful R0 resection, we observed a higher MPR rate (41.4%, 12/29) in three-cycle group compared with two-cycle group (26.9%, 7/26) (p = 0.260), meanwhile, pCR rate achieved 24.1% (7/29) and 19.2% (5/26) respectively (p = 0.660). Patients of squamous subtype generally achieved a statistically higher MPR rate (51.6%, 16/31) compared with the non-squamous subtype (12.5%, 3/24) (p = 0.002). In squamous subgroup, three cycles neoadjuvant treatment induced a MPR rate of 60% compared with 43.8% after two cycles treatment (p = 0.366).In the meantime, the MPR rate was 21.4% versus 0% in non-squamous subgroup, respectively (p = 0.239). The ORR showed no statistical difference between three-cycle group (55.2%, 16/29) and two-cycle (50%, 13/26) (p = 0.701). Patients were well-tolerated in both groups and 5% (3/60) experienced grade 3 immune related adverse events. Conclusions: It is the first randomized study comparing different treatment periods of immuno-chemotherapy in the neoadjuvant setting. Three cycles neoadjuvant treatment achieved a numerically higher MPR rate compared with two cycles. Patients with squamous lung cancer obtained a better MPR rate compared with non-squamous subtype. Clinical trial information: NCT04459611.

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