Programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitor has become one of the important treatment options for patients with advanced non-small cell lung cancer (NSCLC). However, only a small subset of patients with NSCLC can currently receive single-agent PD-1 inhibitors as first-line therapy, for the limitations of population selection exclude most patients from immuno-oncology (IO) monotherapy. In order to expand the candidate population for IO first-line treatment and make more newly diagnosed patients benefit from IO treatment, a series of studies are focusing on the combination of IO and other drugs in NSCLC. We reviewed the latest clinical data of IO first-line combination therapy in recent years, suggesting that on the basis of PD-1/PD-L1 inhibitors, combined with other IO, chemotherapy, anti-angiogenic drugs, targeted therapy or radiotherapy may produce synergistic anti-tumor effects. It is expected to benefit more newly diagnosed patients.
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Animals ; Carcinoma, Non-Small-Cell Lung ; immunology ; therapy ; Humans ; Immunotherapy ; methods ; trends ; Lung Neoplasms ; immunology ; therapy

In recent years, the checkpoint inhibitors targeted programmed cell death 1 (PD-1) and its ligand 1 (PD-1 ligand, PD-L1) achieved landmark significance in treating a variety of cancers including non-small cell lung cancer (NSCLC). However, current immunotherapy is not precise enough, only 15%-20% of the unselected patients can benefit from the therapy, and there is a possibility of hyperprogression (HP). Therefore, how to select the dominant population is crucial. Although many studies have emphasized the importance of PD-L1 and tumor mutation burden (TMB) and other indicators to guide immunotherapy, current PD-L1 expression level and mutation load cannot be used as a decisive and excluded predictive marker based on various obstacles. With the deepening of research, we found that there is a close relationship between lung cancer-driver gene mutation and aberrant activation of PD-1/PD-L1 signal pathways, and the correlation between gene mutation and immunotherapy efficacy has broad research value. This article will revolve around the above issues.
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Carcinoma, Non-Small-Cell Lung ; genetics ; immunology ; therapy ; Humans ; Immunotherapy ; methods ; Lung Neoplasms ; genetics ; immunology ; therapy ; Treatment Outcome

Cryptococcus neoformans commonly causes opportunistic infections in immunocompromised patients, especially in patients with AIDS. CD4+ T-lymphocytopenia in AIDS indicates an increased risk of opportunistic infection and a decline in immunological function. Idiopathic CD4 T-lymphocytopenia (ICL) is characterized by depletions in the CD4+ T-cell subsets, without evidence of HIV infection. Immunodeficiency can exist in the absence of laboratory evidence of HIV infection, and T-cell subsets should be evaluated in patients who present with unusual opportunistic infections. We report a case of pulmonary cryptococcosis and lung cancer in a patient with persistently low CD4+ cell counts, without evidence of HIV infection.
Aged ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/*pathology ; Carcinoma, Non-Small-Cell Lung/*complications/immunology ; Cryptococcosis/*complications/immunology ; Humans ; Lung Neoplasms/*complications/immunology ; Lymphopenia/*complications/immunology ; Male

OBJECTIVETo explore the impact on neutrophil-to-lymphocyte ratio (NLR) and the quality of life (QOL) in the patients of non-small-cell lung cancer (NSCLC) treated with wheat-size moxibustion therapy.

METHODSSeventy patients of NSCLC were randomized into an observation group and a control group, 35 cases in each one. Finally, 33 cases were participated in the observation group and 32 cases in the control group for statistical analysis. In the observation group, Zusanli (ST 36) and Feishu (BL 13) were selected for grain-size moxibustion, 9 moxa cones on each acupoint, once a day. There was the follow-up visit without any treatment applied in the control group. The trial lasted for 6 weeks. The changes in NLR and the QOL score before and after treatment were observed in the patients of the two groups and the differences were compared between the two groups.

RESULTSCompared with the condition before treatment, in the observation group, NLR was reduced apparently (P< 0.05), the general health state/life quality field, physical functioning, emotional functioning, cognitive functioning, fatigue, pain, short breath, insomnia and anorexia were improved apparently (all P < 0.05). In the control group, the differences were not significant in NLR, the general health states/life quality field, physical functioning, emotional functioning, cognitive functioning, role functioning, social functioning, fatigue, pain, short breath, insomnia and anorexia before and after treatment (all P > 0.05). In comparison of the two groups, NLR was reduced apparently in the observation group as compared with that in the control group after treatment (P < 0.05). The scores of the general health state/life quality field, physical functioning, emotional functioning and cognitive functioning were increased apparently as compared with those in the control group after treatment (all P < 0.05). The scores of fatigue, pain, short breath, insomnia and anorexia in the observation group were reduced apparently as compared with those in the control group after treatment (all P < 0.05).

CONCLUSIONThe wheat-size moxibustion therapy reduces NLR and improves the immune function and quality of life in the patients of NSCLC.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; immunology ; therapy ; Female ; Humans ; Lung Neoplasms ; immunology ; therapy ; Lymphocytes ; immunology ; Male ; Middle Aged ; Moxibustion ; Neutrophils ; immunology ; Quality of Life

The purpose of this study is to evaluate the clinical significance of E-cadherin expression in lung cancer. E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1). Strongly positive (++) E-cadherin tumors were classified as a type of preserved E-cadherin expression (Pr type), while the others (+, - tumors) were classified as a type of reduced E-cadherin expression (Rd type). The frequency of Pr type in squamous cell carcinomas (59.0%) was higher than Rd type. However, in adenocarcinomas, the frequency of Rd type was higher than Pr type. E-cadherin expression pattern was significantly correlated with differentiated state (Pearson correlation coefficient 0.394, p>0.001). E-cadherin expression of well-differentiated tumors was more frequently preserved than that of poorly differentiated tumors (60.0% vs. 25.9%). With regard to the correlation between E-cadherin expression and stages of lymph node metastasis in non-small cell lung cancers, the percentage of tumors with Pr type E-cadherin expression declined from 66.3% (> or = N1) to 38.6% (> or = N2), indicating that loss of E-cadherin expression is responsible for acquisition of invasive potential of lung cancer as well as the possible role of E-cadherin in the histological differentiation of lung cancer.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Cadherins/immunology ; Cadherins/biosynthesis* ; Cadherins/analysis* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/chemistry ; Female ; Human ; Immunohistochemistry ; Lung Neoplasms/pathology* ; Lung Neoplasms/metabolism ; Lung Neoplasms/chemistry ; Lymph Nodes/pathology ; Male ; Middle Age ; Predictive Value of Tests ; Prognosis

Objective: To investigate the effects of derived neutrophil to lymphocyte ratio (dNLR) and lung immune prognostic index (LIPI) score on the overall survival (OS) of non-surgical elderly non-small cell lung cancer (NSCLC) patients. Methods: Clinical and pathological data of NSCLC patients in Hebei General Hospital from January 2014 to June 2018 were collected retrospectively. The dNLR value was calculated based on the results of blood routine before treatment, and the optimal cut-off value of dNLR was obtained by ROC curve. The patients were divided into low dNLR level group and high dNLR level group based on the optimal dNLR cut-off value. The groups were classified as good, intermediate and poor based on the LIPI score consisting of lactate dehydrogenase (LDH) and dNLR tested before treatment. The Kaplan-Meier method and Log rank test were used for survival analysis, and the Cox risk proportional regression model was used for analysis of prognostic influences. Results: The area under the ROC curve for dNLR predicting prognosis in non-surgical elderly NSCLC patients was 0.591 (95% CI: 0.491, 0.692; P=0.093). The optimal cut-off value for dNLR predicting prognosis in elderly NSCLC patients was 2.515, with a sensitivity of 45.5% and a specificity of 81.8%. The gender, BMI, pathological type and degree of tumor differentiation were associated with dNLR levels (P<0.05). The median survival times were 16 and 10 months for patients in the low dNLR level group (dNLR<2.51) and high dNLR level group (dNLR≥2.51), respectively (P<0.001), and 15, 10 and 6 months for patients with good, intermediate and poor LIPI scores, respectively (P<0.001). The age, gender, smoking, pathological type, tumor differentiation, clinical stage, BMI, dNLR level, LDH level and LIPI scores were all associated with patient prognosis (P<0.05), and age≥76 years, tumor differentiation and clinical stage Ⅲ and Ⅳ were independent factors influencing patient prognosis (P<0.05). Conclusion: No matter what treatment measures are taken, dNLR level and LIPI score are related to patients' prognosis, and non-surgical elderly NSCLC patients with high dNLR level and poor LIPI score before treatment have worse prognoses.
Aged ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; L-Lactate Dehydrogenase ; Lung Neoplasms/drug therapy* ; Lymphocytes/immunology* ; Neutrophils/immunology* ; Prognosis ; Retrospective Studies

OBJECTIVETo study the relation of tumor interstitial T lymphocyte subset activity to the clinical staging of non-small-cell lung cancer (NSCLC) and the immune response.

METHODSImmunohistochemical staining for CD4(+), CD8(+) and CD4(+)CD25(+) Foxp3(+) (regulatory T cells, Treg) T cells was performed on paraffin-embedded tissues from 60 NSCLC cases.

RESULTSCompared to stage I/II NSCLC patients, patients in stage III/IV showed a significant decrease in the percentage of CD4(+) and CD4(+)/CD8(+) T cells (P<0.05) and an increase in CD8(+) and CD4(+)CD25(+) Foxp3(+) T cells (P<0.05). Treg cells were enriched in the tumor tissue as compared with those in the adjacent tissues.

CONCLUSIONSThe proportion of CD4(+)CD25(+) Foxp3(+) Treg cells is positively correlated to the clinical staging of NSCLC, in which T cell-mediated immune response is suppressed.

Aged ; Carcinoma, Non-Small-Cell Lung ; immunology ; pathology ; Female ; Humans ; Lung ; immunology ; Lung Neoplasms ; immunology ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; T-Lymphocyte Subsets ; immunology ; T-Lymphocytes, Regulatory ; immunology

Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.
Animals ; Carcinoma, Non-Small-Cell Lung ; immunology ; therapy ; Cell Line, Tumor ; ErbB Receptors ; immunology ; metabolism ; Female ; Humans ; Immunotherapy, Adoptive ; methods ; Lung Neoplasms ; immunology ; therapy ; Mice ; Mice, Inbred NOD ; Receptors, Chimeric Antigen ; immunology ; T-Lymphocytes ; immunology ; Xenograft Model Antitumor Assays

Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%–20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immuno-oncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC.
Allergy and Immunology ; Carcinoma, Non-Small-Cell Lung ; Cell Cycle Checkpoints ; Drug Therapy ; Humans ; Immune System ; Immunotherapy ; Lung Neoplasms ; Standard of Care ; Survival Rate

OBJECTIVETo observe the clinical therapeutic effect and mechanism of Yiqi Yangyin Jiedu Decoction (YYJD, a Chinese herbal recipe for strengthening qi, nourishing yin and removing toxic substance, consisting of milkvetch root 30 g, glehnia root 30 g, asparagus root 15 g, lilyturf root 15 g, grossy privet fruit 12 g, spikemoss herb 30 g, Chinese sage herb 30 g, manyleaf paris rhizome 30 g, etc. ) in treating patients with advanced nonsmall cell lung cancer (NSCLC).

METHODSSixty patients with advanced lung cancer of qi-yin deficiency syndrome were randomized into three groups: the TCM group (A) treated with YYJD, the chemotherapy group (B) treated by chemotherapy with NP or GP protocol, and the combined treated group (C) treated with YYJD and chemotherapy in combination. The efficacy was evaluated after two cycles of treatment.

RESULTSThe total effective rate for alleviating qi-yin deficiency syndrome in group A was 80%, significantly higher than that in Group C and B (35% and 20%, P <0.01) respectively. The KPS increasing and stabilizing rate in Group A and C was 90% and 85% respectively, significantly higher than that in Group B (75%), and difference between A and B was significant (P <0.05). In Group C after treatment, CD(3)+ showed a rising trend (P = 0.05), different to that in Group A and B (P <0.05 and P <0.01); CD(4)+ significantly increased (P <0.05) and CD(4)+/CD(8)+ ratio showed increasing trend (P = 0.06), while in Group B both were decreased significantly, showed significantly difference (P < 0.05). CD(8)+ CD(28)+ significantly increased after treatment in Group A and C (P <0.01 and P <0.05), but showed decreasing trend (P = 0.06) in Group B, significant difference was shown between B and C (P <0.05).

CONCLUSIONYYJD can ameliorate the qi-yin deficiency syndrome evidently in advance lung cancer patients; improve their quality of life, the mechanism might be by way of enhancing T-lymphocyte activity and killer T-cell function, to elevate the T-cell mediated immunity in a round way.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; immunology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; T-Lymphocytes ; drug effects ; immunology ; Treatment Outcome