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Colon tumors with deficient DNA mismatch repair (dMMR) are generally infiltrated by T cells more densely than tumors with proficient mismatch repair (pMMR). However, high numbers of tumor-infiltrating lymphocytes (TILs) are found in select pMMR tumors, and low numbers of TILs are seen in select dMMR tumors. In this study, we compared T-cell repertoires in 20 pMMR and 27 dMMR colon tumors with high and low TIL counts. We found that T cells in dMMR tumors are more clonal and their repertoire is less rich compared with T cells in pMMR tumors. In the dMMR group, T cells in TIL-high tumors were more clonal and their repertoire was less rich compared with T cells in TIL-low tumors, but in the pMMR group, T-cell diversity in TIL-high tumors was comparable to T-cell diversity in TIL-low tumors. These findings suggest that T cells clonally expand in dMMR tumors, possibly in response to MMR deficiency-induced tumor neoantigens.

Background: Greater quadriceps strength has been associated with lower risk of symptomatic knee osteoarthritis (OA) in older adults. However, factors that confer elevated risk of knee OA (eg, sedentary lifestyle, obesity, and knee injury) also contribute to a reduced tolerance of resistance training programs at ≥60% 1-repetition maximum (1RM). Therefore, the current study assessed whether concurrent application of blood flow restriction (BFR) to low-load resistance training is an efficacious and tolerable means of improving quadriceps strength in men at risk of symptomatic knee OA. Methods: Men older than age 45, with a history of knee injury or elevated body mass index (BMI), were randomized to low-load resistance training (30% 1RM) either with or without concurrent BFR. Isotonic double-leg press strength and isokinetic knee extensor strength were assessed before and after 4 weeks of training 3 times/wk. Knee pain (Knee Osteoarthritis Outcome Score) was assessed for tolerance. Results: Of the 42 men (mean age 56.1 ± 7.7 years) who were randomized, 41 completed the program. There were no significant intergroup differences in age, BMI, knee pathology, or muscle strength at baseline. Although leg press 1RM improved in both control and BFR groups, there were no significant intergroup differences in primary or secondary measures of muscle strength. The BFR was not associated with worsening of knee pain, but there was a significant improvement in knee pain in the control group. Conclusions: In comparison with training without BFR, addition of BFR to 30% 1RM resistance training for 4 weeks did not confer significantly greater increases in leg press or quadriceps strength in older men with risk factors for symptomatic knee OA.