BackgroundImmunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 μg LPP administered subcutaneously over 3 weeks.MethodsIn a randomized, double‐blind, placebo‐controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 μg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) was assessed as secondary endpoints.ResultsThe mean reduction in CSMS in the LPP vs placebo group was −15.5% (P = .041) during the peak period and −17.9% (P = .029) over the entire pollen season. LPP‐treated group had a reduced reactivity to CPT (P < .001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score (P = .005) compared with placebo group. Mostly mild and WAO grade 1 early systemic reaction (ESR) were observed ≤30 minutes in 10.5% of LPP‐treated patients, whereas 3 patients with a medical history of asthma (<1%) experienced a serious ESR that resolved with rescue medication.Conclusion Lolium perenne pollen peptides administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms and was generally safe and well‐tolerated.

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There is increasing evidence that the effect of chemotherapy on tumor growth is not cell autonomous but relies on the immune system. The objective of this study was therefore to decipher the cellular and molecular mechanisms underlying the role of innate and adaptive immunity in chemotherapy-induced tumor rejection. Treatment of DBA/2 mice bearing P815 mastocytoma with cyclophosphamide induced rejection and long-term protection in a CD4-and CD8-dependent manner. A population of inflammatory-type dendritic cells was dramatically expanded in the lymph nodes of mice that rejected the tumor and correlated with CD4-dependent infiltration, in tumor bed, of tumor-specific CD8 1 T lymphocytes. Our data point to a major role of CD4 1 T cells in inducing chemokine expression in the tumor, provoking migration of tumor-specific CXCR3 1 CD8 1 T lymphocytes. Importantly, the analysis of CD8 1 T cells specific to P1A/H-2L d and P1E/H-2K d revealed that cyclophosphamide altered the P815-specific CD8 T repertoire by amplifying the response specific to the mutated P1E antigen.Increasing evidence suggests that tumor infiltration by T lymphocytes is a good prognostic factor for cancer patients. The prognostic and predictive impact of the immune infiltrates has been demonstrated in colorectal, ovarian, breast cancers and melanomas.

The majority of rodent and human tumors express antigens that can be recognized by T lymphocytes and are infiltrated by immune cells. Although tumor infiltration by T lymphocytes has been associated with a favorable prognosis, the role of dendritic cells (DCs), which may present tumor-associated antigens in an immunogenic or tolerogenic context, remains elusive. Here, we discuss recent observations suggesting that the function of DCs in the tumor microenvironment may impact the spontaneous resistance of neoplasms to chemotherapy as well as treatment outcome.

RATIONALE: Human olfactory mucosa-derived mesenchymal stem cells (hOM-MSCs) are promising for treatment of immune diseases. The immunomodulatory activities of hOM-MSCs are partially ascribed to CD4 + T and B-lymphocytes, macrophages, and dendritic cells. The effect of the hOM-MSCs on function of CD8 + cytotoxic lymphocytes (CTLs) and natural killer cells (NKCs) was assessed. METHODS: hOM-MSC were generated from biopsies of patients (n53) with non-inflammatory diseases of the nasal cavity. Peripheral blood mononuclear cells (PBMCs) (n57) were cultured over hOM-MSCs in 10:1 ratio for 3 days. Expression of perforin, granzyme B and CD107a were analyzed in both CTLs and NKCs subsets. Jurkat cells were used as target cells. PBMCs and Jurkat were co-cultured in a 5:1 ratio for 2 h. Necrosis and apoptosis were detected by Annexin V (FITC) / To-PRO-3 staining. RESULTS: The hOM-MSCs reduced granzyme B and perforin expression in NKCs, but not in CTLs. The hOM-MSCs suppressed both spontaneous and tumor cell-stimulated degranulation detected by CD107a expression in both CTLs and NKCs. The Viability assay showed that hOM-MSC-treated PBMCs possessed reduced ability to induce apoptosis in target cells (MSCs-treated group-22.2 [range 18.2-27.3]%, control-13.3 [range 12.0-15.4]%; p50.02). CONCLUSIONS: hOM-MSCs suppressed cytotoxic functions of CTLs and NKCs affecting expression of perforin, granzyme B, CD107a, which eventually led to the reduced ability to induce apoptosis in target tumor cells. The development of MSC-based cell therapy may be useful for diseases associated with excessive cytotoxicity.