Alveolar macrophages activated with concanavalin A and peripheral blood monocytes activated with lipopolysaccharide secrete type fi transforming growth factor (TGF-j6). There is minimal TGF-/3 secretion in unactivated monocytes, even though TGF-4 mRNA is expressed in these cells at a level similar to that in activated, lipopolysaccharidetreated cultures. U937 lymphoma cells, which have monocytic characteristics, also express mRNA for TGF-j3. Freshly isolated monocytes, both control and lipopolysaccharide-treated, secrete an acid-labile binding protein that inhibits TGF-,B action. We conclude the following: (i) that expression of TGF-1B mRNA is unrelated to monocyte activation, (ii) that secretion of TGF-fJ is induced by monocyte activation, and (iii) that cosecretion of TGF-13 and its monocyte/macrophage-derived binding protein may modulate growth factor action. In contrast, monocytic expression of other growth factor genes, such as the B chain of platelet-derived growth factor, is not constitutive and requires activation.Type , transforming growth factor (TGF-,l) (1-5), a peptide widely distributed in tissues of humans and other animals, has the unusual ability both to stimulate and inhibit the proliferation of cells in culture (6-10). Although the effect of TGF-,B on epithelial cells is consistently inhibitory (6, 7, 9), its role in mesenchymal cell proliferation is more complex (7,8,11). For example, TGF-,3 acts synergistically with epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) to stimulate mitosis of normal rat kidney (NRK) and smooth muscle cells cultured in soft agar yet antagonizes the effect of these mitogens by inhibiting mitosis of the same cells cultured as subconfluent monolayers (7,8,12,13 3 (8).A second cell type that acts as an important source of growth factors during tissue repair in vivo is the macrophage (18). This cell, which appears in healing wounds prior to the onset of a fibrotic response (19,20), is a paracrine source of growth factors. This paracrine role of macrophages during wound repair in vivo can be demonstrated in studies that show that fibrosis is suppressed when monocyte infiltration is blocked (21). Since activated macrophages are known to secrete PDGF (22-24), the present studies were designed to see if macrophages might also be a paracrine source of TGF-P. Both PDGF and TGF-,3 may have important roles in stimulating smooth muscle cell proliferation in atherogenesis (25) as well as in fibroblastic proliferation in connective tissue repair (13, 16). MATERIALS AND METHODSIsolation and Activation of Human Alveolar Macrophages. Alveolar macrophages were obtained by bronchoalveolar lavage of normal nonsmoking human volunteers; samples typically contained >90% alveolar macrophages, -8% lymphocytes, and <1% polymorphonuclear leukocytes (26). Alveolar macrophages were suspended (106 cells per ml) in serum-free medium [MCDB 104/Dulbecco Vogt phosphatebuffered saline (PBS), 1:1 (vol/vol); Irvine Scientific and GIBCO, respectively] supplemented with bov...

The response rate to immune checkpoint inhibitor therapy for non-small-cell lung cancer (NSCLC) is just 20%. To improve this figure, several early phase clinical trials combining novel immunotherapeutics with immune checkpoint blockade have been initiated. Unfortunately, these trials have been designed without a strong foundational knowledge of the immune landscape present in NSCLC. Here, we use a flow cytometry panel capable of measuring 51 immune cell populations to comprehensively identify the immune cell composition and function in NSCLC. The results show that the immune cell composition is fundamentally different in lung adenocarcinoma as compared with lung squamous cell carcinoma, and that neutrophils are the most prevalent immune cell type. Using T-cell receptor-β sequencing and tumour reactivity assays, we predict that tumour reactive T cells are frequently present in NSCLC. These results should help to guide the design of clinical trials and the direction of future research in this area.

IPS remains a frequently fatal complication that limits the broader use of allogeneic HSCT as a successful treatment modality. Faced with the clinical syndrome of IPS, one can categorize the disease entity with the appropriate tools, although cases of unclassifiable IPS will remain. Significant research efforts have resulted in a paradigm shift away from identifying noninfectious lung injury after HSCT solely as an idiopathic clinical syndrome and toward understanding IPS as a process involving aspects of both the adaptive and the innate immune response. Importantly, new laboratory insights are currently being translated to the clinic and will likely prove important to the development of future strategies to prevent or treat this serious disorder.

To describe the clinical presentation and progression of obstructive lung disease after marrow transplantation, we examined a sequential sample of 35 patients who had allogeneic marrow transplantation between January 1980 and January 1987, were 16 years or older, had normal pulmonary function tests before transplantation, and developed airflow obstruction defined as FEV1/FVC less than 70% and FEV1 less than 80% predicted 50 days or more after transplantation. Cases were selected from 1029 adult (older than 16 years) patients who underwent allogeneic marrow transplantation during the same period. Patients with airflow obstruction presented with symptoms of cough, dyspnea, or wheezing, or a combination. In 80% the chest radiograph was normal. Airflow obstruction was diagnosed within 1.5 years after transplantation in 33 of 35 patients. Clinical, extensive, chronic graft-versus-host disease was present in 24 patients. Only 4 patients had a complete response to primary therapy of chronic graft-versus-host disease. Serum IgG and IgA levels were decreased in 15 and 25 patients, respectively. The FEV1 declined rapidly (decrease in FEV1 greater than 30% between tests) in 21 patients, but 14 patients with slowly progressive or reversible disease were identified. Mortality was 65% at 3 years after transplant, a significantly higher value (P = 0.016) than the 3-year mortality rate of 44% in a comparison group of 412 concurrent patients with chronic graft-versus-host disease who were 16 years or older, survived more than 80 days after transplantation, and had normal pulmonary function. We concluded that obstructive lung disease after marrow transplantation may be variable with respect to time of onset and rate of progression. Obstructive lung disease was frequently associated with serum immunoglobulin deficiency and clinical, extensive, chronic graft-versus-host disease that was not readily responsive to treatment. Mortality was high but long-term survivors were identified.