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Memory CD8+ T cells populate non-lymphoid tissues (NLTs) following pathogen infection, but little is known about the establishment of endogenous tumor-specific tissue-resident memory T cells (T RM ) during cancer immunotherapy. Using a transplantable mouse model of prostate carcinoma, here we report that tumor challenge leads to expansion of naïve neoantigen-specific CD8+ T cells and formation of a small population of non-recirculating T RM in several NLTs. Primary tumor destruction by irreversible electroporation (IRE), followed by anti-CTLA-4 immune checkpoint inhibitor (ICI), promotes robust expansion of tumor-specific CD8+ T cells in blood, tumor, and NLTs. Parabiosis studies confirm that T RM establishment following dual therapy is associated with tumor remission in a subset of cases and protection from subsequent tumor challenge. Addition of anti-PD-1 following dual IRE + anti-CTLA-4 treatment blocks tumor growth in non-responsive cases. This work indicates that focal tumor destruction using IRE combined with ICI is a potent in situ tumor vaccination strategy that generates protective tumor-specific T RM .

A comprehensive programmatic computer simulation planning model for a school of medicine was generated by integrating several separate simulation models with on-site cost study information. An elementary validation of the model was achieved. The model generated program costs in terms of both faculty hours and dollars. Results indicated that the size of the medical class could be increased from 75 to 100 students within the present resource limitations by transferring faculty time to education from other programs. The maximum class size was limited by the availability of clinical material. The basic science departments could handle this class size easily without significant reduction in other programs, but the clinical departments could not do so unless inpatient levels increased significantly.

The relationship of cervical colonization of genital mycoplasmas and infection with cytomegalovirus (CMV) was studied in 66 intrauterine device (IUD) users as contrasted to 60 patients using oral contraception and 50 patients using neither an IUD nor oral contraception. No significant increase in colonization or genital mycoplasmas or infection with CMV was noted in IUD users. No CMV was isolated from users of the cooper-t IUD. It is unlikely that genital mycoplasmas are related to either the increased immunoglobulin levels seen in patients using the IUD or the antifertility effects of the IUD.

Twenty-five patients with chronic bronchitis were studied intensively from 1968 to 1972. Viral, bacteriologic, mycologic, and mycoplasmal studies, both serologic and cultural, were carried out in an attempt to determine the role these agents play in exacerbations. All of the usual viral agents associated with exacerbations and 2 members of the coronavirus group, 229E and OC43, were detected. One third (33.6 per cent) of the 116 exacerbations observed could be related to viral infection or Mycoplasma pneumoniae (1 exacerbation). Viral infection was also noted to occur during periods of remission but was more commonly associated with periods of exacerbation(P less than 0.001). No interrelationship between viral and bacterial infection was apparent and neither Streptococcus pneumoniae nor Haemophilus influenzae was present more frequently in the sputum of patients in exacerbation. However, the number of S. pneumoniae organisms present in the sputum was significantly greater (P=0.04) during exacerbation than during remission and their presence was significatnly correlated with increases sputum purulence (P LESS THAN 0.01). This was not true of H. influenzae. Ampicillin was effective in clearing the sputum of S. pneumoniae but not of H. influenzae; the reverse was true of tetracycline.

In this article the authors present the findings of a study of the process by which medical schools' internal information systems respond to external questionnaires. A representative sample of six medical schools was selected for the study, which was conducted under the joint auspices of the Association of American Medical Colleges and the Bureau of Health Manpower, Department of Health, Education, and Welfare. The process for completing four national questionnaires was analyzed following site visits and detailed documentation at each school. An overall objective of the study was to estimate the effect of this process on the quality of data supplied. A number of problems with the process which inhibited the provision of reliable data were found. These are highlighted and corrective action suggested both for the institutions completing the questionnaire and for the sponsoring agencies.

Forsyth, Ben R. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), Helen V. Coates, and Robert M. Chanock. Biophysical studies of respiratory syncytial virus. II. Identification of two soluble complement-fixing antigens of respiratory syncytial virus. J. Bacteriol. 91:1270-1276. 1966.-Column chromatography of concentrated preparations was used to separate two antigenic components from the "soluble complement-fixing (CF) antigen" of respiratory syncytial (RS) virus. These antigens, designated antigen A and antigen B, stimulated homologous but not heterologous CF antibodies. Only antigen A stimulated the production of neutralizing antibody in guinea pigs. There was a dissociation between the CF and neutralizing antibody responses of guinea pigs immunized with antigen A. The two antigens were shown to have different molecular size, density, and sensitivity to lipolytic agents. Both antigens appeared to be components of the RS viral particle. Serological studies demonstrated that both antigens were formed during RS virus infection of children and adults.

Dans, P. E. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), B. R. Forsyth, and R. M. Chanock. Density of infectious virus and complement-fixing antigens of two rhinovirus strains. J. Bacteriol. 91:1605-1611. 1966.-Two rhinovirus serotypes (echovirus 28 and HGP) and poliovirus type 1 were banded by isopycnic centrifugation in cesium chloride. The rhinovirus virions had a density of 1.41 g/ml, whereas that of poliovirus was 1.34. Since a number of other enteroviruses also have a density of 1.34 g/ml in cesium chloride, a basic difference in density may exist between the rhinovirus and enterovirus subgroups of the picornavirus family. Whether this difference reflects differences in ribonucleic acid content or binding of cesium ions remains to be determined. In tests with echovirus 28 two peaks of CF activity were detected: one in association with the virion (1.41 g/ml), and a larger peak of lower density (1.30 g/ml). With echovirus 28 antiserum, a heterotypically reactive complement-fixing (CF) antigen was detected in the HGP virus suspension at a density less than that of the virion (1.30 g/ml). This antigen corresponded in density to the less dense CF antigen of echovirus 28.

Coates, Helen V. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), Ben R. Forsyth, and R. M. Chanock. Biophysical studies of respiratory syncytial virus. I. Density of respiratory syncytial virus and associated complement-fixing antigens in a cesium chloride density gradient. J. Bacteriol. 91:1263-1269. 1966.-Concentrated fluids from respiratory syncytial (RS) virus-infected tissue cultures (HEp-2 and BEK) were subjected to equilibrium sedimentation in cesium chloride. When two antigenically distinct strains of RS virus (Long and 18537) were tested, approximately 90% of the infectious virus was recovered in a sharp, symmetrical peak with a density of 1.22 to 1.24. In a similar study, unconcentrated virus had a density of 1.25 to 1.27. Two immunologically distinguishable complement-fixing antigens (antigens A and B) were detected at densities of 1.28 to 1.32 and 1.23 to 1.37. In addition, the existence of a third antigen (density of 1.22 to 1.30) was suggested. The possible origin of these antigens is discussed relative to the known properties of RS virus and the other myxoviruses.

Gentamicin is a more effective in vitro bacterial inhibitor than combined penicillinstreptomycin, is nontoxic to tissue culture monolayers, and does not inhibit virus replication.